Method of pacing a heart using implantable device

ABSTRACT

A method of determining an optimal location for implanting a pacemaker electrode includes the steps of pacing a heart from a first location and generating a first map of the heart associated with pacing at the first location. The heart is paced from a second location and a second map is generated of the heart associated with pacing at the second location. The first and second maps are compared in order to diagnose the effect of the pacing and an optimal location for implanting the pacemaker electrode based on the comparison of the maps is selected.

FIELD OF THE INVENTION

[0001] The present invention relates to the field of cardiac medicineand more particularly to diagnosing and treating diseased hearts basedon the interaction between cardiac electro-physiological and cardiacbio-mechanical activity.

BACKGROUND OF THE INVENTION

[0002] Cardiovascular diseases accounted for approximately 43 percent ofthe mortality in the United States of America in 1991 (923,000 persons).However, many of these deaths are not directly caused by an acutemyocardial infraction (AMI). Rather, many patients suffer a generaldecline in their cardiac output known as heart failure. Once the overtsigns of heart failure appear, half the patients die within five years.It is estimated that between two and three million Americans suffer fromheart failure and an estimated 200,000 new cases appear every year. Inmany cases heart failure is caused by damage accumulated in thepatient's heart, such as damage caused by disease, chronic and acuteischemia and especially (˜75%) as a result of hypertension.

[0003] A short discussion of the operation of a healthy heart is usefulin order to appreciate the complexity of the functioning of the heartand the multitude of pathologies which can cause heart failure. FIG. 1Ais a schematic drawing of a cross-section of a healthy heart 20. Ingeneral heart 20 comprises two independent pumps. One pump comprises aright atrium 22 and a right ventricle 24 which pump venous blood from aninferior and a superior vena cava to a pair of lungs (not shown) to beoxygenated. Another pump comprises a left atrium 26 and a left ventricle28, which pump blood from pulmonary veins (not shown) to a plurality ofbody systems, including heart 20 itself The two ventricles are separatedby a ventricular septum 30 and the two atria are separated by an atrialseptum 32.

[0004] Heart 20 has a four phase operational cycle in which the twopumps are activated synchronously. FIG. 1B shows a first phase, calledsystole. During this phase, right ventricle 24 contracts and ejectsblood through a pulmonic valve 34 to the lungs. At the same time, leftventricle 28 contracts and ejects blood through an aortic valve 36 andinto an aorta 38. Right atrium 22 and left atrium 26 are relaxed at thispoint and they begin filling with blood, however, this preliminaryfilling is limited by distortion of the atria which is caused by thecontraction of the ventricles.

[0005]FIG. 1C shows a second phase, called rapid filling phase andindicates the start of a diastole. During this phase, right ventricle 24relaxes and fills with blood flowing from right atrium 22 through atricuspid valve 40, which is open during this phase. pulmonic valve 34is closed, so that no blood leaves right ventricle 24 during this phase.Left ventricle 28 also relaxes and is filled with blood flowing fromleft atrium 26 through a mitral valve 42, which is open. Aortic valve 36is also closed to prevent blood from leaving left ventricle 26 duringthis phase. The filling of the two ventricles during this phase isaffected by an existing venous pressure. Right atrium 22 and left atrium26 also begin filling during this phase. However, due to relaxation ofthe ventricles, their pressure is lower than the pressure in the atria,so tricuspid valve 40 and mitral valve 42 stay open and blood flows fromthe atria into the ventricles.

[0006]FIG. 1D shows a third phase called diastatis, which indicates themiddle of the diastole. During this phase, the ventricles fill veryslowly. The slowdown in filling rate is due to the equalization ofpressure between the venous pressure and the intra-cardiac pressure. Inaddition, the pressure gradient between the atria and the ventricles isalso reduced.

[0007]FIG. 1E shows a fourth phase called atrial systole which indicatesthe end of the 15 diastole and the start of the systole of the atriaDuring this phase, the atria contract and inject blood into theventricles. Although there are no valves guarding the veins entering theatria, there are some mechanisms to prevent backflow during atrialsystole. In left atrium 26, sleeves of atrial muscle extend for one ortwo centimeters along the pulmonary veins and tend to exert asphincter-like effect on the veins. In right atrium 22, a crescenticvalve forms a rudimentary valve called the eustachian valve which coversthe inferior vena cava In addition, there may be muscular bands whichsurround the vena cava veins at their entrance to right atria 22.

[0008]FIG. 1F is a graph showing the volume of left ventricle 24 as afunction of the cardiac cycle. FIG. 1F clearly shows the additionalvolume of blood injected into the ventricles by the atria during atrialsystole as well as the variance of the heart volume during a normalcardiac cycle. FIG. 1G is a graph which shows the time derivative ofFIG. 1F, i.e., the left ventricle fill rate as a function of cardiaccycle. In FIG. 1G two peak fill rates are shown, one in the beginning ofdiastole and the other during atrial systole.

[0009] An important timing consideration in the cardiac cycle is thatthe atrial systole must complete before the ventricular systole begins.If there is an overlap between the atrial and ventricular systoles, theatria will have to force blood into the ventricle against a raisingpressure, which reduces the volume of injected blood. In somepathological and induced cases, described below, the atrial systole isnot synchronized to the ventricular systole, with the effect of a lowerthan optimal cardiac output.

[0010] It should be noted that even though the left and the right sidesof heart 20 operate in synchronization with each other, their phases donot exactly overlap. In general, right atrial systole starts slightlybefore left atrial systole and left ventricular systole starts slightlybefore right ventricular systole. Moreover, the injection of blood fromleft ventricle 26 into aorta 38 usually begins slightly after the startof injection of blood from right ventricle 24 towards the lungs and endsslightly before end of injection of blood from right ventricle 24. Thisis caused by pressures differences between the pulmonary and bodycirculatory systems.

[0011] When heart 20 contracts (during systole), the ventricle does notcontract in a linear fashion, such as shortening of one dimension or ina radial fashion. Rather, the change in the shape of the ventricle isprogressive along its length and involves a twisting effect which tendsto squeeze out more blood. FIG. 2 shows an arrangement of a plurality ofmuscle fibers 44 around left ventricle 28 which enables this type ofcontraction. When muscle fibers 44 are arranged in a spiral manner asshown in FIG. 2 and the activation of muscle fibers 44 is started froman apex 46 of left ventricle 28, left ventricle 28 is progressivelyreduced in volume from the bottom up. The spiral arrangement of musclefibers 44 is important because muscle fibers typically contract no morethan 50% in length. A spiral arrangement results in a greater change ofleft ventricular volume than is possible with, for example, a flatarrangement in which the fibers are arranged in bands around the heart.An additional benefit of the spiral arrangement is a leverage effect. Ina flat arrangement, a contraction of 10% of a muscle fiber translatesinto a reduction of 10% of the ventricular radius. In a spiralarrangement with, for example, a spiral angle 48 of 45°, a 10%contraction translates into a 7.07% contraction in ventricular radiusand a 7.07% reduction in ventricular length. Since the ventricularradius is typically smaller than the ventricular length, the net resultis that, depending on spiral angle 48, a tradeoff is effected between agiven amount of contraction and the amount of force exerted by thatcontraction.

[0012] Spiral angle 48 is not constant, rather, spiral angle 48 changeswith the distance of a muscle fiber from the outer wall of theventricle. The amount of force produced by a muscle fiber is a functionof its contraction, thus, each layer is optimized to produce an optimalamount of force. Since the contraction of each muscle fiber issynchronous with the increase in the ventricular pressure (caused by themuscle contraction), it might be expected that the muscle fibers producea maximum force at maximum contraction. However, physiologicalconstraints on muscle fibers denote that maximal force is generatedbefore maximal contraction. In addition, the force exerted by a musclefiber begins to fall soon after maximum force is exerted. The varyingspiral angle is a mechanism which makes it possible to increase thecontractile force on the ventricle after maximum force is reached by aparticular muscle fiber.

[0013] As described above, activation of the heart muscle is from theapex up. Thus, the muscle on the top of the ventricle couldtheoretically exert more force than the muscle at apex 46, which wouldcause a distention at apex 46. The varying spiral angle is one mechanismto avoid distention. Another mechanism is that the muscle near apex 46,which is activated first, is slightly more developed than the muscle atthe top of the ventricle, which is activated last. As a result of theabove described mechanisms, the force exerted by the ventricular wall ismore evenly distributed over time and space. It should be appreciatedthat blood which remains in one place without moving, even in the heart,can clot, so it is very important to eject as much blood as possible outof the heart.

[0014] As can be appreciated, a complicated mechanism is required tosynchronize the activation of muscle fibers 44 so that an efficient fourphase cycle is achieved. This synchronization mechanism is provided byan electrical conduction system within the heart which conducts anelectrical activation signal from a (natural) cardiac pacemaker tomuscle fibers 44.

[0015]FIG. 3 shows the main conduction pathways in heart 20. An SA node50, located in right atrium 22, generates an activation signal forinitiating contraction of muscle fibers 44. The activation signal istransmitted along a conduction pathway 54 to left atria 26 where theactivation signal is locally disseminated via bachman bundles and Cristaterminals. The activation signal for contracting the left and rightventricles is conducted from SA node 50 to an AV node 52, where theactivation signal is delayed. The ventricles are normally electricallyinsulated from the atria by non-conducting fibrous tissue, so theactivation signal must travel through special conduction pathways. Aleft ventricle activation signal travels along a left pathway 58 toactivate left ventricle 28 and a right ventricle activation signaltravels along a right pathway 56 to activate right ventricle 24.Generally, the conduction pathways convey the activation signal to apex46 where they are locally disseminated via purkinje fibers 60 andpropagation over the rest of the heart is achieved by conduction inmuscle fibers 44. In general, the activation of the heart is from theinner surface towards the outer surface. It should be noted thatelectrical conduction in muscle fibers 44 is generally faster along thedirection of the muscle fibers. Thus, the conduction velocity of theactivation signals in heart 20 is generally anisotropic.

[0016] As can be appreciated, the delay in AV node 52 results, in ahealthy heart, in proper ventricular systolic sequencing. The temporaldistribution of the activation signal in the ventricular muscle resultsin the activation of the ventricles from the apex up. In a healthy heartthe activation signal propagates across left ventricle 28 inapproximately 60 milliseconds. In an externally paced heart, where theactivation signal is not conducted through purkinje fibers 60 or in adiseased heart, the propagation time is typically longer, such as 150milliseconds. Thus, disease and external pacing affect the activationprofile of the heart.

[0017] Cardiac muscle cells usually exhibit a binary reaction to anactivation signal; either the cell responds normally to the activationsignal or it does not respond at all. FIG. 4 is a graph showing changesin the voltage of a single cardiac muscle cell in reaction to theactivation signal. The reaction is generally divided into five stages. Arapid depolarization stage 62 occurs when the muscle cell receives anactivation signal. During this stage, which lasts a few milliseconds,the potential of the cell becomes rapidly positive. Afterdepolarization, the muscle fiber rapidly repolarizes during a rapidrepolarization stage 64 until the cell voltage is approximately zero.During a slow repolarization stage 66, also known as the plateau, themuscle cell contracts. The duration of stage 66, the plateau duration,is directly related to the amount of work performed by the muscle cell.A relatively fast repolarization stage 68 follows, where the muscle cellrepolarizes to its original potential. Stage 66 is also known as therefractory period, during which the cell cannot be activated by anotheractivation signal. During stage 68, the cell is in a relative refractoryperiod, during which the cell can be activated by an exceptionallystrong activation signal. A steady state 70 follows in which the musclecell is ready for another activation.

[0018] It should be appreciated that the contraction of cardiac musclecells is delayed in time from their activation In addition the durationof the contraction is generally equal to the duration of the plateau.

[0019] An important factor which may affect the length of the plateau isthe existence of an ionic current resulting from the voltage potentialsgenerated by the local depolarizations. The ionic current starts at thelast activated portion of the heart and progresses back along the pathof the activation. Thus, it is the later activated portions of the heartwhich are first affected by the ionic current. As a result, therepolarization of these cells is relatively faster than therepolarization of the first activated muscle fibers, and theircontraction time is relatively shorter. As can be appreciated, in ahealthy heart, where the propagation time of the activation signal isrelatively short, the ionic currents are significantly smaller than in adiseased or externally paced heart.

[0020] One of the main results of the contraction of the ventricles isincreased intra-ventricular pressure. In general, when the intra-cardiacpressure is higher, the outflow from the heart into the circulatorysystem is stronger and the efficiency of the heart is higher. Amathematical relationship termed Laplace's law can be used to model therelationship between the pressure in the ventricle and the tension inthe wall of the ventricle. Laplace's law was formulated for generallyspherical or cylindrical chambers with a distentible wall, however, thelaw can be applied to the ventricles since they are generally elongatedspherical in shape. FIGS. 5A-C show three formulations for determiningthe tension in a portion of the ventricle wall, all of which are basedof the law of Laplace. In FIG. 5A, the tension across a cross-section ofthe wall is shown wherein T, the tension in the wall, is equal to theproduct of p, the transmural pressure across the wall, r (squared), theradius of the ventricle, and π. FIGS. 5B and C show formulas forcalculating the tension per unit in portions of the ventricular wall,for example in FIG. 5C, for a unit cross-sectional area of muscle in awall of thickness δ.

[0021] As can be appreciated, if r, the radius of the ventricle, islarge, a higher tension is needed to produce the same pressure change asin a ventricle with a smaller radius. This is one of the reasons thatventricular dilation usually leads to heart failure. The heart muscle isrequired to produce a higher tension is order to achieve the samepressure gradient. However, the heart is not capable of producing therequired tension, so, the pressure gradient, and thus the cardiacefficiency, are reduced.

[0022] Unfortunately, not all people have healthy hearts and vascularsystems. Some types of heart problems are caused by disease. HCM(hypertrophic cardiomyopathy or HOCM) is a disease in which the leftventricle and, in particular, the ventricular septum, hypertrophy,sometimes to an extent which blocks the aortic exit from the leftventricle. Other diseases, such as atrophy causing diseases, reduce theamount of muscle fibers in portions of the heart.

[0023] A very common cause of damage to the heart is ischemia of theheart muscle. This condition, especially when manifesting itself as anacute myocardial infraction (heart attack), can create dead zones in theheart which do not contain active muscle. An additional, and possiblymore important effect, is the non-conducting nature of these dead zoneswhich may upset the natural activation sequence of the heart. In somecases, damaged heart tissue continues to conduct the activation signal,albeit at a variable or lower velocity, which may cause arrhythmias.

[0024] A chronic ischemic condition is usually caused by blockage of thecoronary arteries, usually by arteriosclerosis, which limits the amountof oxygen which can reach portions of the heart muscle. When more work(i.e., more tension) is required of the heart muscle and an increase inoxygen supply is not available, the result is acute pain, and if thesupply is cut off for an extended period, death of the starved musclewill follow.

[0025] When the output of the heart is insufficient, a common result ishypertrophy of the heart, usually of the left ventricle. Hypertrophy isa compensatory mechanism of the heart for increasing the output volume.However, in a chronic condition, hypertrophy has generally negativeeffects. For example, arrhythmias, congestive heart failure (CHF) andpermanent changes in the morphology of the heart muscle (ventricularmodeling) may result from hypertrophy.

[0026] One of the most common cardio-vascular diseases is hypertension.A main effect of hypertension is increased cardiac output demand, whichcauses hypertrophy since the blood must be pumped against a higherpressure. Furthermore, hypertension usually aggravates other existingcardiac problems.

[0027] The human heart has many compensatory and adaptive mechanisms,termed cardiac reserve, so that not all cardiac pathologies manifest asheart disease. Once the cardiac reserve is used up, the heart cannotkeep up with the demand and heart failure may result. One measure ofheart function and efficiency is the left ventricle ejection factor,which is the ratio between the amount of blood in the left ventricleduring diastole and the amount of blood exiting during systole. Itshould be noted that a significant portion of the change in ventricularvolume between systole and diastole is due to the thickening ofactivated muscle fibers. Another measure of heart function is the leftventricle stroke volume, which is the amount of blood which is ejectedfrom the left ventricle each heart beat. It should be noted that oncethe cardiac reserve is used up it is difficult, if not impossible, forthe heart to increase its output when needed, such as during exercise.

[0028] There are many ways in which non-optimal timing of the activationof the heart can result in lower cardiac output. In AF (atrialfibrillation) one or both atria does not contract in correct sequencewith its associated ventricle. As a first result, the atria does notinject blood into its associated ventricle during atrial systole, so theventricle volume is not maximized before ventricular systole, and strokevolume is slightly reduced. If the right atria is fibrillating,sequencing of the AV node is non-regular, which results in theventricles contracting at an irregular rate, and the heart output isfurther reduced.

[0029] In some cases of a conduction block between the SA node and theventricles, such as caused by a damaged AV node, the contraction of theatria is not synchronized to the contraction of the ventricles, whichalso results in a lower heart output.

[0030] Another type of timing deficiency results when there are largedead areas in the heart muscle which do not conduct electrical signals.The activation signal must circumvent the dead areas, which results in alonger pathway (and longer delay time) for the activation signalreaching some portions of the heart. In some cases, these portions ofthe heart are activated long after the rest of the heart has alreadycontracted, which results in a reduced contribution of these portions tothe total cardiac output.

[0031] Heart muscle which is stressed before it is activated, heartmuscle which is weakened (such as by ischemia) and portions of the heartwhich have turned into scar tissue, may form aneurysms. As can beappreciated from Laplace's law, portions of the ventricle wall which donot generate enough tension to offset the tension induced by theintra-cardiac pressure must increase their local radius in response tothe pressure overload. The stretched wall portion thins out and mayburst, resulting in the death of the patient. The apex of the leftventricle is especially susceptible to aneurysms since it may be verythin. In addition, the total pressure in the ventricle and the flow fromthe ventricle arc reduced as the aneurysm grows, so the heart output isalso reduced. Although weak muscle should be expected to hypertrophy inresponse to the greater need, in some cases, such as after an AMI,hypertrophy may not occur before irreversible tissue changes are causedby the stretching.

[0032] Perfusion of the heart muscle usually occurs during diastole.However, if the diastole is very long, such as when the activationsignal is propagated slowly, some portions of the heart may not beoxygenated properly, resulting in functional ischemia

[0033] As mentioned above, one of the adaptation mechanisms of the heartis hypertrophy, in which the size of the heart increases to answerincreased demand. However, hypertrophy increases the danger of aarrhythmias, which in some cases reduce heart output and in others, suchas VF (ventricular fibrillation) are life threatening. Arrhythmias arealso caused by damaged heart tissues which generate erroneous activationsignals and by blocks in the conduction system of the heart.

[0034] In some cases arrhythmias of the heart are treated usingmedicines, in others, by implanting a pacemaker or a defibrillator. Acommon pacemaker implanting procedure, for example for treating theeffects of AF, includes:

[0035] (a) ablating or removing the AV node; and

[0036] (b) implanting a pacing electrode in the apex of the heart. Thelocation of the pacing electrode may be changed (during the procedure)if the heart does not beat at a desired sequence for a given output ofthe pacemaker.

[0037] It is also known to pace using multiple electrodes, where theactivation signal is initiated from a selected one or more of theelectrodes, depending on sensed electrical values, such as sequence,activation time and depolarization state. Typically, the pacing regimeis adapted to a specific arrhythmia. Sometimes, logic is included in thepacemaker which enables it to identify and respond to several types ofarrhythmia

[0038] U.S. Pat. No. 5,403,356 to Hill et al. describes a method ofpreventing atrial arrhythmias by adapting the pacing in the right atriumin response to a sensed atrial depolarization, which may indicate anarrhythmia

[0039] Sometimes the pacing is performed for more than one chamber. Forexample, in dual chamber pacing, both left and right ventricles areseparately paced. There have been attempts to use dual chamber pacing torelive aortic obstruction caused by HCM. The aortic exit from the leftventricle is located between the left and right ventricle, so that whenboth ventricles contract simultaneously, the aorta is squeezed from allsides. In a healthy heart, the ventricular septum does not obstruct theaorta, however, in an HCM-diseased heart, the enlarged septum obstructsthe aortic exit from the left ventricle. When pacing to reduce aorticobstruction, the contractions of the left and right ventricles arestepped, so that when the left ventricle contracts, the right ventricledilates and the aorta is less compressed.

[0040] Lameh Fananapazir, Neal D. Epstein, Rodolfo V. Curiel, Julio A.Panza, Dorothy Tripodi and Dorothea McAreavey, in “Long-Term Results OfDual-Chamber (DDD) Pacing In Obstructive Hypertrophic Cardiomyopathy ”,Circulation, Vol. 90, No. 60, pp. 2731-2742, Dec. 1994, the disclosureof which is incorporated herein by reference, describes the effects ofpacing a HCM-diseased heart using DDD pacing at the apex of the rightventricle. One effect is that the muscle mass near the pacing locationis reduced, i.e., the ventricular septum is atrophied. The atrophy ishypothesized to be caused by the changes in workload at the pacedlocation which are due to the late activation time of ventricularsegments far from the pacing location.

[0041] Margarete Hochleitner, Helmut Hortnagl, Heide Hortnagl, LeoFridrich and Franz Gschnitzer, in “Long-Term Efficiency Of physiologicDual-Chamber pacing In The Treatment Of End-Stage Idiopathic DilatedCardiomyopathy”, American Journal of Cardiology, volume 70, pp.1320-1325, 1992, the disclosure of which is incorporated herein byreference, describes the effect of DDD pacing on hearts which aredilated as a result of idiopathic dilated cardiomyopathy. DDD pacingresulted in an improvement of cardiac function and in a reduction inhypertrophy in several patients. In addition, it is suggested thatpositioning the ventricular electrode of the DDD pacemaker in near theapex of the right ventricle reduced the stress at the apex of the leftventricle, by its early activation. No method is suggested for choosingthe implantation location of the electrodes.

[0042] Xavier Jeanrenaud, Jean-Jacques Goy and Lukas Kappenberger, in“Effects Of Dual Chamber Pacing In Hypertrophic ObstructiveCardiomyopathy”, The Lancet, Vol. 339, pp. 1318-1322, May 30, 1992, thedisclosure of which is incorporated herein by reference, teaches that toensure success of DDD pacing in HCM diseased hearts, an optimum AVinterval (between atrial activation and ventricular activation) isrequired. In addition, it is suggested that this optimal AV interval ismodified by performing exercise.

[0043] Several methods may be used to treat heart failure. One method isto connect assist pumps to the patient's circulatory system, whichassist the heart by circulating the blood. To date, no satisfactorylong-term assist pump has been developed. In some cases, a diseasedheart is removed and replaced by another human heart However, this is anexpensive, complicated and dangerous operation and too few donor heartsare available. Artificial hearts suffer from the same limitations asassist pumps and, like them, are not yet practical.

[0044] Certain types of heart failure, such as those caused byconduction blocks in the AV node or by AF can be helped by theimplantation of a pacemaker, as described above.

[0045] Some cases of heart failure can be helped by medicines whicheither strengthen the heart, correct arrhythmias or reduce the totalvolume of blood in the body (which reduces blood pressure); However,many cases of heart failure can only be treated by reducing the activityof the patient. Ultimately, once the cardiac reserve is used up, mostcases of heart failure cannot be treated and result in death.

[0046] U.S. Pat. No. 5,391,199, the disclosure of which is incorporatedherein by reference, discloses apparatus and method for mapping theelectrical activity of the heart.

[0047] “Biomedical Engineering Handbook”, ed. Joseph D. Bronzino,chapter 156.3, pp. 2371-2373, IEEE press/CRC press, 1995, describesmodeling strategies in cardiac physiology. On page 2373 a model isdescribed, including experimental support, according to which model theshape of a ventricle is determined by the (local) amount of oxygenconsumption. In addition, this model differentiates between pressureoverload on the heart, which causes thickening of muscle fibers, denotedconcentric hypertrophy, and volume overload which causes an increase inthe ventricular volume (by stretching), denoted eccentric hypertrophy.Eccentric hypertrophy may also be caused by reducing the amount ofoxygen available to the cardiac muscle.

[0048] R. S. Reneman, F. W. prinzen, E. C. Cheriex, T. Arts and T.Delhass, in “Asymmetrical Changes in Left Ventricular Diastolic WallThickness Induced by Chronic Asynchronous Electrical Activation in Manand Dogs”, FASEB J., 1993;7;A752 (abstract), abstract number 4341, thedisclosure of which in incorporated herein by reference, describeresults of studies in paced hearts and which show that earlier activatedventricular wall portions were thinner than later activated wallportions, showing an asymmetrical hypertrophy as a result of the pacing.

[0049] C. Daubert, P H. Mabo, Veronique Berder, D. Gras and C. LeClercq,in “Atrial Tachyarrhythmias Associated with High Degree InteratrialConduction Block: Prevention by Permanent Atrial Resynchronisation”,European Journal of C.P.E, Vol. 4, No. 1, pp. 35-44, 1994, thedisclosure of which is incorporated herein by reference, describes amethod of treating atrial fibrillation by implanting pacemakerelectrodes in various locations in the heart, including two electrodesin the right atrium.

[0050] Frits W. Prinzen, Cornelis H. Augustijn, Theo Arts, Maurits A.Allessie and Robert Reneman, in “Redistribution of Myocardial FiberStrain and Blood Flow by Asynchronous Activation”, American Journal ofPhysiology No. 259 (Heart Circulation Physiology No. 28), H300-H308,1990, the disclosure of which is incorporated herein by reference,describes studies which show that the location of pacing electrodes in apaced heart significantly affect the distribution of strain, andperfusion (blood flow) in the heart.

SUMMARY OF THE INVENTION

[0051] It is an object of some aspects of the present invention toprovide methods of augmenting the compensatory mechanisms of the heart.

[0052] Another object of some aspects of the present invention is toprovide methods of mapping the local physiological values and/or theshape of the heart to determine the activation profile of the heart and,preferably, to analyze the resulting maps to determine possibleoptimizations in the activation profile.

[0053] Yet another object of some aspects of the present invention is tocontrol the adaptation mechanisms in the heart so that the heart outputor some other parameter of the heart is optimized. Alternatively oradditionally, the adaptation mechanisms of the heart are utilized toeffect change in the morphology of the hear t such as by redistributingmuscle mass.

[0054] Still another object of some aspects of the present invention isto control the activation sequence of the heart so that the heart outputor some other physiological variable of the heart is optimized,preferably, in real-time.

[0055] When used herein, the terms “physiological variable” and “cardiacparameter” do not include electrical activity, rate, arrhythmia orsequencing of the heart. The term “local physiological value” does notinclude electrical activity, per se, rather it refers to a localphysiological state, such as contraction of local heart muscle,perfusion or thickness. The term “location” refers to a location on orin an object, such as the heart muscle. For example, a valve or an apexof the heart. “Position” refers to a position in space, usually relativeto a known portion of the heart, for example, 1.5 inches perpendicularfrom the apex of the heart.

[0056] The term “local information” includes any information associatedwith the location on the heart wall, including position and electricalactivity.

[0057] An object of some aspects of the present invention is related topacemakers which are adapted to control the adaptation mechanisms of theheart and/or to optimize heart parameters.

[0058] In a preferred embodiment of the invention, the mechanical motionof the heart muscle is mapped using a catheter having a position sensornear its distal end. The mapping includes:

[0059] (a) placing the catheter into contact with the heart wall;

[0060] (b) determining the position of the distal end of the catheter,and

[0061] (c) repeating step (b) for additional locations in the heart.

[0062] Preferably, the catheter is in contact with the heart wallthrough the entire cardiac cycle. It should be appreciated that contactwith the heart wall can be achieved either from the inside or from theoutside 6f the heart, such as outside contact being achieved byinserting the catheter into the coronary arteries and/or veins.Alternatively, the catheter is directly inserted into the body (notthrough the vascular system), such as through a throactoscope or duringsurgery.

[0063] Preferably, (b) includes determining the position of the catheterat at least two instants of an entire heart cycle. More preferably, itincludes determining the position with time over the cycle.Alternatively or additionally, the catheter has a plurality of distalends, each with a position sensor and (b) includes determining theposition of each one of the ends.

[0064] Preferably, the catheter does not move between sequentialdiastoles. This can be asserted, for example, by using an impedancesensor, by determining changes in a locally sensed electrogram, bydetermining that the position sensor repeats its trajectory during heartcycles or by determining that the catheter returns to the same locationeach diastole or other recognizable portion of the cardiac cycle.

[0065] Preferably, the mapping further includes determining the geometryand/or changes in the geometry of at least a portion of the heart as afunction of time and/or phase of the cardiac cycle. For example, theexistence of an aneurysm can be determined from a characteristic bulgeof the aneurysm during systole. Likewise, a dilated ventricle can bedetermined from the determined volume. Additionally or alternatively,the mapping includes determining the local radius of a portion of theheart wall.

[0066] Preferably the catheter comprises a pressure sensor whichmeasures the intra-cardiac pressure. Further preferably, the forces onthe heart wall are calculated using the local radius and/or thedetermined pressure, preferably using Laplace's law.

[0067] Preferably, the catheter includes at least one electrode fordetermining the local electrical activity of the heart. Preferably, thelocal activation time and/or the activation signal is measured andincorporated in a map of the heart. Additionally or alternatively, localelectrical conductivity is measured, since fibrous scar tissue does notconduct as well as viable muscle tissue.

[0068] A preferred embodiment of the invention provides a map whichcompares the local activation time to the movement of a segment of localheart wall. Preferably, the map compares activation time of the segmentto movement of the segment relative to the movement of surroundingsegments. Thus, the reaction of a muscle segment to the activationsignal can be determined from the local geometrical changes.

[0069] In a preferred embodiment of the invention, the instantaneousthickness of the heart wall at the point of contact is also determined.Preferably, the thickness is measured using an ultrasonic transducer,preferably mounted on the distal portion of the catheter. Preferably,changes in the thickness of the cardiac wall are used to determine thereaction of the heart muscle to the activation signal. Typically, whenthe muscle contracts, the wall thickens, while if the muscle does notreact and the intra-cardiac pressure rises, the wall thins.

[0070] In a preferred embodiment of the invention provides a map of thelocal energy expenditure of the heart. Preferably, the local energyexpenditure is determined using Laplace's law, local changes inthickness and a pressure sensor, mounted on the catheter, whichdetermines the intra-cardiac pressure.

[0071] In preferred embodiments of the invention, additional oralternative sensors are mounted on the distal end of the catheter andare used in constructing cardiac maps. For example, a Doppler ultrasonicsensor which measures perfusion may be used to determine the localperfusion as a function of time and workload. Additionally oralternatively, an ionic sensor is used to sense changes in ionconcentrations.

[0072] Although the above maps are described as being time based orcardiac-phase based, in a preferred embodiment of the invention,measurements are binned based on geometrical characteristics of theheart or on ECG or electrogram characteristics. Preferably, the ECGcharacteristics comprise pulse rate and /or ECG morphology. Mapsassociated with different bins can be compared to determine pathologiesand under utilization of the heart, for example, an abnormal activationprofile due to a conduction abnormality, such as a block, for assessingthe effects of tachycardia or for assessing changes in the activationprofile as a function of heart rate.

[0073] Preferably, maps constructed before a cardiac procedure arecompared to maps constructed after a procedure to determine the effectof the procedure. In some instances, maps of the heart are constructedwhile the heart is artificially paced.

[0074] A preferred embodiment of the invention provides for changing thedistribution of muscle-mass in the heart from an existing muscle-massdistribution to a desired muscle-mass distribution. This is achieved byadjusting the pacing of the heart to achieve an activation profile whichaffects such change. Preferably, portions of the heart which arerelatively atrophied are activated so that relatively more effort isrequired of them than previously. Alternatively or additionally,portions of the heart which are hypertrophied are activated so that lesseffort is required of them than previously. Preferably, the decision howto change the activation profile of the heart is based on a map of thehear further preferably, using a map which shows the local energyexpenditure and/or the local work performed by each portion of theheart. Alternatively or additionally, a map which shows the ratiobetween local perfusion and local energy expenditure is used.Preferably, the activation profile of the heart is changed when theheart approaches the desired muscle mass distribution. Typically, theheart is paced using an implanted pacemaker. Preferably, a map is usedto determine the optimal location for the pacing electrode(s).Additionally or alternatively, a treatment course of pharmaceuticals foraffecting the activation of the heart, may be designed using such a mapand a model of the reaction of the heart to the pharmaceuticals.

[0075] Other cardiac treatment options may also be planned and/ordecided between using such maps. For example, bypass surgery is only anoption if the unperfused tissue (whose ischemia will be relived by thesurgery), is viable and its activity (and contribution to the heart)will be improved by the surgery. Thus, before deciding between bypasssurgery, PCTA and other reperfusion treatments, it is possible toacquire and analyze a map to help with the decision. In one example,tissue which induces arrhythmia due to ischemia can be detected using amap of the types described herein and a decision to reperfuse made. Inanother example, performing bypass surgery to increase perfusion to scartissue, is traumatic to the patient and may actually reduce theperfusion of other parts of the heart. If, before the surgery, a map isconsulted, unnecessary surgery may be averted or at least reduced incomplexity (double instead of triple bypass)

[0076] One aspect of the invention relates to the optimal placement ofpacemaker electrodes. A preferred method of determining electrodeplacement includes:

[0077] (a) pacing a heart from a first location;

[0078] (b) determining a value of a physiological variable while pacingat the first location;

[0079] (c) repeating (a) and (b) at least at a second location; and

[0080] (d) implanting the pacing electrode at a location of the firstand second locations which yields an optimal value for the physiologicalvariable or at a location with a response known to yield an optimalvalue in the future.

[0081] One preferred physiological variable is the stroke volume.Preferably, the physiological variable is measured using a catheter.

[0082] Yet another aspect of the invention relates to pacing a heart toreduce stress. A preferred method of pacing the heart includes:

[0083] (a) measuring a local physiological value at a plurality oflocations in the heart;

[0084] (b) determining a pacing regime which will change thedistribution of the value at the plurality of locations; and

[0085] (c) pacing the heart using the new pacing regime.

[0086] Preferably, the new pacing regime is determined such that thestress on certain portions of the heart will be reduced, preferably, bykeeping the local physiological value within a range. Furtherpreferably, the range is locally determined based on local conditions inthe heart. One preferred local physiological value is blood perfusion.Preferably, (a)-(c) are performed substantially in real time. Furtherpreferably, measuring the physiological value is performed substantiallysimultaneously at the plurality of locations.

[0087] Still another aspect of the invention relates to increasing theefficiency of a heart using adaptive pacing. A preferred method ofadaptive pacing includes:

[0088] (a) determining a preferred pacing regime for a heart which isoptimal with respect to a physiological variable; and

[0089] (b) pacing the heart using the preferred pacing regime.

[0090] Preferably, the preferred pacing regime is determined using a mapof the heart. The map is preferably analyzed to determine which portionsof the heart are under-utilized due to their activation time. Thepreferred pacing is preferably initiated by implanting a pacer,preferably, with a plurality of electrodes. Alternatively oradditionally, the preferred pacing is initiated by changing theelectrification of a plurality of previously implanted pacemakerelectrodes.

[0091] In a preferred embodiment of the invention, the pacing regime isregularly changed so that each pacing regime optimizes the utilizationof different portions of the heart. Additionally or alternatively, thepacing regime is regularly changed to temporally distribute workloadbetween different portions of the heart.

[0092] Another aspect of the invention relates to pacemakers havingadaptive pacing regimes. A preferred pacemaker includes:

[0093] a plurality of electrodes;

[0094] a source of electricity for electrifying the electrodes; and

[0095] a controller which changes the electrification of the electrodesin response to a plurality of measured local physiological values of aheart to achieve an optimization of a physiological variable of theheart.

[0096] The measured physiological values preferably include plateaulength and/or activation time. Preferably, the measurement is performedusing the pacemaker electrodes. Alternatively or additionally,measurement is performed using at least one additional sensor. Onepreferred physiological variable is stroke volume. Further preferably,the physiological variable is measured by the pacemaker, such asmeasuring intra-cardiac pressure using a solid-state pressure sensor.

[0097] There is therefore provided in accordance with a preferredembodiment of the invention, a method of constructing a cardiac map of aheart having a heart cycle including:

[0098] (a) bringing an invasive probe into contact with a location on awall of the heart;

[0099] (b) determining, at at least two different phases of the heartcycle, a position of the invasive probe;

[0100] (c) determining a local non-electrical physiological value at thelocation;

[0101] (d) repeating (a)-c) for a plurality of locations of the heart;and

[0102] (e) combining the positions to form a time-dependent map of atleast a portion of the heart. Preferably, the method includes:

[0103] (f) determining at least one local relationship between changesin positions of the invasive probe and a determined local non-electricalphysiological value.

[0104] There is provided in accordance with another preferred embodimentof the invention, a method of constructing a cardiac map of a hearthaving a heart cycle including:

[0105] (a) bringing an invasive probe into contact with a location on awall of the heart;

[0106] (b) determining a position of the invasive probe;

[0107] (c) determining a local non-electrical physiological value at thelocation at a plurality of different phases of the heart cycle;

[0108] (d) repeating (a)-(c) for a plurality of locations of the heart;and

[0109] (e) combining the positions to form a map of at least a portionof the heart. Preferably, the method includes determining at least asecond position of the invasive probe at a phase at which the localnon-electrical value is found, which position is different from theposition determined in (b). Preferably, the method includes determiningat least one local relationship between changes in positions of theinvasive probe and determined local non-electrical physiological values.

[0110] Preferably, the method includes determining a trajectory of theprobe as a function of the cardiac cycle. Preferably, the methodincludes analyzing the trajectory.

[0111] Additionally or alternatively, the local physiological value isdetermined using a sensor external to the probe. Preferably, the sensoris external to a body which includes the heart. Alternatively, the localphysiological value is determined using a sensor in the invasive probe.Alternatively or additionally, the local physiological value isdetermined at substantially the same time as the position of theinvasive probe. Alternatively or additionally, the map includes aplurality of maps, each of which corresponds to a different phase of thecycle of the heart. Alternatively or additionally, the map includes adifference map between two maps, each of which corresponds to adifferent phase of the cycle of the heart. Alternatively oradditionally, the local physiological value includes a chemicalconcentration.

[0112] Alternatively or additionally, the local physiological valueincludes a thickness of the heart at the location. Preferably, thethickness of the heart is determined using an ultrasonic transducermounted on the invasive probe. Preferably, the method includesdetermining a reaction of the heart to an activation signal by analyzingchanges in the thickness of the heart.

[0113] Alternatively or additionally, the local physiological valueincludes a measure of a perfusion at the location. Alternatively oradditionally, the local physiological value includes a measure of workperformed at the location. Alternatively or additionally, the methodincludes determining a local electrical activity at each of theplurality of locations of the heart. Preferably, the electrical activityincludes a local electrogram. Alternatively or additionally, theelectrical activity includes a local activation time. Alternatively oradditionally, the electrical activity includes a local plateau durationof heart tissue at the location. Alternatively or additionally, theelectrical activity includes a peak-to-peak value of a localelectrogram.

[0114] Alternatively or additionally, the method includes determining alocal change in the geometry of the heart. Preferably, the local changeincludes a change in a size of an area surrounding the location.Alternatively or additionally, the local change includes a warp of anarea surrounding the location. Alternatively or additionally, the localchange includes a change in a local radius of the heart at the location.Preferably, the method includes determining an intra-cardiac pressure ofthe heart. Preferably, the method includes determining a relativetension at the location. Preferably, the relative tension is determinedusing Laplace's law.

[0115] In a preferred embodiment of the invention, the method includesdetermining an absolute tension at the location.

[0116] In a preferred embodiment of the invention, the method includesdetermining a movement of the location on the heart wall relative to themovement of neighboring locations. Alternatively or additionally, themethod includes determining the activity of the heart at the location.Preferably, determining the activity includes determining a relativemotion profile of the location on the heart wall relative to neighboringlocations. Alternatively, the activity includes determining a motionprofile of the heart at the location.

[0117] In a preferred embodiment of the invention, the method includesmonitoring stability of the contact between the invasive probe and theheart. Preferably, monitoring includes monitoring the stability of thecontact between the probe and the heart based on the motion profile.Alternatively or additionally, monitoring includes detecting changes inthe motion profile for different heart cycles. Alternatively oradditionally, monitoring includes detecting differences in positions ofthe probe at the same phase for different heart cycles. Alternatively oradditionally, monitoring includes detecting changes in a locallymeasured impedance of the invasive probe to a ground. Alternatively oradditionally, monitoring includes detecting artifacts in a locallydetermined electrogram.

[0118] In a preferred embodiment of the invention, the method includesreconstructing a surface of a portion of the heart Alternatively oradditionally, the method includes binning local information according tocharacteristics of the cycle of the heart. Preferably, thecharacteristics include a heart rate. Alternatively or additionally, thecharacteristics include a morphology of an ECG of the heart. Preferably,the ECG is a local electrogram. Alternatively or additionally, themethod includes separately combining the information in each bin into amap. Preferably, the method includes determining differences between themaps.

[0119] In a preferred embodiment of the invention, the positions of theinvasive probe are positions relative to a reference location.Preferably, the reference location is a predetermined portion of theheart. Alternatively or additionally, a position of the reference isdetermined using a position sensor. Alternatively or additionally, themethod includes periodically determining a position of the referencelocation. Preferably, the position of the reference location is acquiredat the same phase in different cardiac cycles.

[0120] In a preferred embodiment of the invention, the invasive probe islocated in a coronary vein or artery. Alternatively, the invasive probeis located outside a blood vessel.

[0121] In a preferred embodiment of the invention, local information isaveraged over a plurality of cycles.

[0122] There is also provided in accordance with a preferred embodimentof the invention, a method of determining the effect of a treatmentincluding constructing a first map of a heart, prior to the treatment;constructing a second map of the heart, after the treatment; andcomparing the first and second maps to diagnose the effect of thetreatment

[0123] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to determine underutilized portions of the heart.

[0124] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to select a procedure for treating the heart.

[0125] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to determine optimization possibilities in the heart.

[0126] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to determine underperfused portions of the heart.

[0127] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to determine over-stressed portions of the heart.

[0128] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to determine local pathologies in the heart.

[0129] There is also provided in accordance with a preferred embodimentof the invention, a method including constructing a map of a heart; andanalyzing the map to assess the viability of portions of the heart.

[0130] There is also provided in accordance with a preferred embodimentof the invention, a method of determining the effect of a change inactivation of a heart, including constructing a first map of a heart,prior to the change; constructing a second map of the heart, after thechange; and comparing the first and second maps to diagnose the effectof the change in activation.

[0131] There is also provided in accordance with a preferred embodimentof the invention, a method of determining the effect of a change inactivation of a heart, including constructing a first map of a heart,prior to the change; constructing a second map of the heart, after thechange; constructing a second map of the heart; and comparing the firstand second maps, wherein the two maps are acquired in parallel byacquiring local information at a location over several cardiac cycles,wherein the activation changes during the several cardiac cycles.

[0132] There is also provided in accordance with a preferred embodimentof the invention, a method of assessing viability including constructinga first map of a heart, prior to a change in activation of the heart;constructing a second map of the heart, after the change; and comparingthe first and second maps to assess the viability of portions of theheart. Preferably, changing the activation includes changing a pacing ofthe heart. Alternatively or additionally, changing the activationincludes subjecting the heart to chemical stress. Alternatively oradditionally, changing the activation includes subjecting the heart tophysiological stress.

[0133] In a preferred embodiment of the invention, the heart isartificially paced.

[0134] There is also provided in accordance with a preferred embodimentof the invention, a method of cardiac shaping including generating a mapof a heart; choosing a portion of the heart having a certain amount ofmuscle tissue thereat; and determining a pacing regime for changing theworkload of the portion. Preferably, the method includes pacing theheart using the determined pacing regime. Preferably, the methodincludes waiting a period of time; then determining the effect of thepacing regime; and repeating choosing, determining and pacing if adesired effect is not reached. Preferably, the workload of the portionis increased in order to increase the amount of muscle tissue therein.Alternatively, the workload of the portion is decreased in order todecrease the amount of muscle tissue thereat. In a preferred embodimentof the invention, the workload is changed by changing an activation timeof the portion. Preferably, the map includes electrical activationinformation. Alternatively or additionally, the map includes mechanicalactivation information.

[0135] There is also provided in accordance with a preferred embodimentof the invention, a method of determining an optimal location forimplanting a pacemaker electrode including:

[0136] (a) pacing a heart from a first location;

[0137] (b) determining a cardiac parameter associated with pacing at thelocation; and

[0138] (c) repeating (a) and (b) for a second location; and

[0139] (d) selecting an optimal location based on the determined valuesfor the cardiac parameters. Preferably, the method includes:

[0140] (e) implanting the electrode at the location for which thecardiac parameter is optimal.

[0141] Preferably, pacing a heart includes bringing an invasive probehaving an electrode to a first location and electrifying the electrodewith a pacing current.

[0142] Preferably, the cardiac parameter includes stroke volume.Alternatively or additionally, the cardiac parameter includesintra-cardiac pressure. Alternatively or additionally, determining thecardiac parameter includes measuring the cardiac parameter using aninvasive probe.

[0143] There is also provided in accordance with a preferred embodimentof the invention, a method of determining a regime for pacing a heart,including:

[0144] (a) determining a local physiological value at a plurality oflocations in the heart; and

[0145] (b) determining a pacing regime which changes a distribution ofthe physiological value in a desired manner. Preferably, thedistribution includes a temporal distribution. Alternatively oradditionally, the distribution includes a spatial distribution.Preferably, the method includes pacing the heart using the determinedpacing regime. Alternatively or additionally, changing the distributionincludes maintaining physiological values within a given range.Preferably, the range includes a locally determined range. Alternativelyor additionally, the range includes a phase dependent range, whereby adifferent range is preferred for each phase of a cardiac cycle.Alternatively or additionally, the range includes an activationdependent range, whereby a different range is preferred for eachactivation profile of the heart. Preferably, different heart rates havedifferent ranges. Alternatively or additionally, different arrhythmiastates have different ranges.

[0146] In a preferred embodiment of the invention, the physiologicalvalues are determined substantially simultaneously. Preferably, thephysiological value includes perfusion. Alternatively or additionally,the physiological value includes stress. Alternatively or additionally,the physiological value includes plateau duration.

[0147] There is also provided in accordance with a preferred embodimentof the invention, a method of determining a preferred pacing regime,including generating a map of the heart; and determining, using the map,a preferred pacing regime for a heart which is optimal with respect to aphysiological variable. Preferably, the method includes pacing the heartusing the preferred pacing regime. Alternatively or additionally, themap includes an electrical map. Preferably, determining a preferredpacing regime includes generating a map of the activation profile of theheart. Alternatively or additionally, the map includes a mechanical map.Preferably, determining a preferred pacing regime includes generating amap of the reaction profile of the heart. Alternatively or additionally,the method includes analyzing an activation map or a reaction map of theheart to determine portions of the heart which are under-utilized due toan existing activation profile of the heart. Alternatively oradditionally, pacing is initiated by implanting at least one pacemakerelectrode in the heart s preferably, the at least one pacemakerelectrode includes a plurality of individual electrodes, each attachedto a different portion of the heart.

[0148] In a preferred embodiment of the invention, pacing is initiatedby changing the electrification of a plurality of previously implantedpacemaker electrodes. Alternatively or additionally, the physiologicalvariable includes a stroke volume. Alternatively or additionally, thephysiological variable includes a ventricular pressure profile.

[0149] There is also provided in accordance with a preferred embodimentof the invention, a method of pacing including:

[0150] (a) pacing a heart using a first pacing scheme; and

[0151] (b) changing the pacing scheme to a second pacing scheme, whereinthe change in pacing is not directly related to a sensed or predictedarrhythmia, fibrillation or cardiac output demand in the heart.Preferably, each of the pacing regimes optimizes the utilization ofdifferent portions of the heart. Alternatively or additionally, thechanging of the pacing regimes temporally distributes workload betweendifferent portions of the heart.

[0152] There is also provided in accordance with a preferred embodimentof the invention, a pacemaker which performs any of the above describedpacing based methods.

[0153] There is also provided in accordance with a preferred embodimentof the invention, a pacemaker including: a plurality of electrodes; asource of electricity for electrifying the electrodes; and a controllerwhich changes the electrification of the electrodes in response to aplurality of values of local information of a heart, measured atdifferent locations, to achieve an optimization of a cardiac parameterof the heart. Preferably, the local information is measured using theelectrodes. Alternatively or additionally, the local information ismeasured using a sensor.

[0154] There is also provided in accordance with a preferred embodimentof the invention, a pacemaker including a plurality of electrodes; asource of electricity for electrifying the electrodes; and a controllerwhich changes the electrification of the electrodes in response to astored map of values of local information of a heart at differentlocations, to achieve an optimization of a cardiac parameter of theheart

[0155] Preferably, the local information includes a local activationtime. Alternatively or additionally, the local information includes alocal plateau duration. Alternatively or additionally, the localinformation includes local physiological values. Alternatively oradditionally, the local information includes phase dependent localpositions. Alternatively or additionally, the cardiac parameter includesa stroke volume. Alternatively or additionally, the cardiac parameter ismeasured by the pacemaker. Alternatively or additionally, the cardiacparameter includes an intra-cardiac pressure.

[0156] There is also provided in accordance with a preferred embodimentof the invention, a method of detecting structural anomalies in a heart,including:

[0157] (a) bringing an invasive probe into contact with a location on awall of the heart;

[0158] (b) determining a position of the invasive probe;

[0159] (c) repeating (a)-(b) for a plurality of locations on the wall;

[0160] (d) combining the positions to form a time-dependent map of atleast a portion of the heart; and

[0161] (e) analyzing the map to determine structural anomalies in theheart. Preferably, the structural anomaly is an insipid aneurysm.

[0162] Preferably, the method includes repeating (b) at least a secondtime, at the same location and at a different phase of the cardiac cyclethan (b).

[0163] There is also provided in accordance with a preferred embodimentof the invention, a method of adding a conductive pathway in a heartbetween a first segment of the heart and a second segment of the heart,including: generating a mechanical map of the heart; providing anactivation conduction device having a distal end and a proximal end;electrically connecting the distal end of the device to the firstsegment; and electrically connecting the proximal end of the device tothe second segment.

[0164] There is also provided in accordance with a preferred embodimentof the invention, a conductive device for creating conductive pathwaysin the heart, including: a first lead adapted for electrical connectionto a first portion of the heart; a second lead adapted for electricalconnection to a second portion of the heart; a capacitor for storingelectrical charge generated at the first portion of the heart and fordischarging the electrical charge at the second portion of the heart.

[0165] There is also provided in accordance with a preferred embodimentof the invention, a method of viewing a map, including: providing a mapof local information of a heart; and overlaying a medical image on themap. Preferably, the medical image is an angiogram. Alternatively oradditionally, the medical image is a three-dimensional image.Alternatively or additionally, the map contains both spatial andtemporal information.

[0166] There is also provided in accordance with a preferred embodimentof the invention, a method of diagnosis including: generating a map of aheart; and correlating the map with a library of maps. Preferably, themethod includes diagnosing the condition of the heart based on thecorrelation.

[0167] There is also provided in accordance with a preferred embodimentof the invention, apparatus including: a memory having a plurality ofmaps stored therein; and a correlator which correlates an input map withthe plurality of maps.

[0168] There is also provided in accordance with a preferred embodimentof the invention, a method of analysis, including generating a map ofelectrical activation of a heart; generating a map of mechanicalactivation of the heart; and determining local relationships between thelocal electrical activation and mechanical activation. Preferably, themechanical activation includes a profile of movement. Preferably, theelectrical activation includes an activation time.

[0169] There is also provided in accordance with a preferred embodimentof the invention, apparatus adapted to generate a map in accordance withany of the mapping methods described herein. Preferably, the apparatusincludes a display adapted to display the map.

[0170] Although the description of the present invention focuses on theheart, apparatus and methods described herein are also useful formapping and affecting other organs, such as the stomach and othermuscles. For example, in treating atrophied muscles using stimulation,an electro-mechanical map of the muscle is preferably acquired during atest stimulation to help in determining and optimal stimulation regime.

BRIEF DESCRIPTION OF THE DRAWINGS

[0171]FIG. 1A is a schematic cross-section diagram of a heart;

[0172]FIG. 1B-1E are schematic cross-section diagrams showing the heartin each of four phases of a cardiac cycle;

[0173]FIG. 1F is a graph showing the blood volume in a left ventricle ofthe heart during a cardiac cycle;

[0174]FIG. 1G is a graph showing the filling rate of the left ventricleduring a cardiac cycle;

[0175]FIG. 2 is a partial schematic view of a heart showing thearrangement of cardiac muscle fibers around a left ventricle; FIG. 3 isa schematic cross-section diagram of a heart showing the electricalconduction system of the heart;

[0176]FIG. 4 is a graph showing changes in the voltage potential of asingle cardiac muscle cell in reaction to an activation signal;

[0177] FIGS. 5A-C are partial schematic cross-sectional perspectiveviews of a heart showing application of Laplace's law to thedetermination of tension in the heart muscle;

[0178]FIG. 6 is a schematic cross-sectional side view of a heart showinga preferred apparatus for generating a map of the heart;

[0179]FIG. 7 is a flowchart of a preferred method of constructing themap utilizing the apparatus of FIG. 6;

[0180]FIG. 8 is a generalized graph showing the dependence of aresistance on the distance of the catheter from heart muscle tissue;

[0181] FIGS. 9A-D show various local changes in the geometry of theheart;

[0182]FIG. 10 shows a multi-headed catheter for sensing local geometricchanges according to a preferred embodiment of the invention;

[0183]FIG. 11 is a flowchart showing a preferred binning method;

[0184]FIG. 12A-D show pathological cases where a change in pacing of aheart is desirable; and

[0185]FIG. 13 is a schematic side view of an implanted pacemakeraccording to a preferred embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0186] A first preferred embodiment of the invention relates to mappingthe geometry of the heart and time related changes in the geometry ofthe heart. FIG. 6 is a schematic side view of a preferred apparatus forperforming the mapping. FIG. 7 is a flowchart showing a preferred methodfor performing a mapping.

[0187] Referring to FIG. 6, a distal tip 74 of a mapping catheter 72 isinserted into heart 20 and brought into contact with heart 20 at alocation 75. Preferably, the position of tip 74 is determined using aposition sensor 76. Sensor 76 is preferably a position sensor asdescribed in PCT application US95/01103, “Medical diagnosis, treatmentand imaging systems”, filed Jan. 24, 1995, in U.S. Pat. No. 5,391,199 orin U.S. Pat. No. 5,443,489, all assigned to the same assignee as theinstant application and the disclosures of which are incorporated hereinby reference, and which typically require an external magnetic fieldgenerator 73. Alternatively, other position sensors as known in the artare used, for example, ultrasonic, RF and rotating magnetic fieldsensors. Alternatively or additionally, tip 74 is marked with a markerwhose position can be determined from outside of heart 20, for example,a radio-opaque marker for use with a fluoroscope. Preferably, at leastone reference catheter 78 is inserted into heart 20 and placed in afixed position relative to heart 20. By comparing the positions ofcatheter 72 and catheter 78, the position of tip 74 relative to theheart can be accurately determined even if heart 20 exhibits overallmotion within the chest. Preferably the positions are compared at leastonce every cardiac cycle, more preferably, during diastole.Alternatively, position sensor 76 determines the position of tip 74relative to catheter 78, for example, using ultrasound, so no externalsensor or generator 73 is required. Alternatively, catheter 78 isoutside the heart, such as outside the body or in the esophagus.

[0188] It should be appreciated that a geometric map can be constructedeven if position sensor 76 only determines position and not orientation.However, since sensor 76 is typically located at a small distance fromtip 74, at least two orientation angles are desirable to increase theaccuracy of the position determination of tip 74.

[0189] Referring to FIG. 7, a typical mapping process includes:

[0190] (a) bringing catheter tip 74 into contact with the wall of heart20, at location 75;

[0191] (b) determining at least one position of tip 74;

[0192] (c) adding the position value to the map;

[0193] (d) moving catheter 72 to a second location, such as a location77;

[0194] (e) repeating steps (b)-(d); and

[0195] (f) (optionally) reconstructing the surface of heart 20 from thedetermined positions.

[0196] Reconstructing the surface of heart 20 may comprisereconstructing inner or outer surfaces of heart 20, depending on thelocation of catheter tip 74. Methods of reconstructing a surface from aplurality of data points are well known in the art

[0197] Preferably, catheter 72 is a steerable tip catheter, so thatrepositioning of tip 74 is facilitated. Steerable catheters are furtherdescribed in PCT application US95/01103 and in U.S. Pat. No. 5,404,297,5,368,592, 5,431,168, 5,383,923, 5,368,564, 4,921,482, 5,195,968, thedisclosures of which are incorporated herein by reference.

[0198] In a preferred embodiment of the invention, each position valuehas an associated time value, preferably relative to a predeterminedpoint in the cardiac cycle. Preferably, multiple position determinationsare performed, at different points in the cardiac cycle, for eachplacement of tip 74. Thus, a geometric map comprises a plurality ofgeometric snapshots of heart 20, each snapshot associated with adifferent instant of the cardiac cycle. The cardiac cycle is preferablydetermined using a standard ECG device. Alternatively or additionally, alocal reference activation time is determined using an electrode oncatheter 72. Heart 20 may be paced in a known manner, such as bycatheter 78 or may be naturally paced.

[0199] In an alternative preferred embodiment of the invention, positionvalues are acquired also while tip 74 is not in contact with heart 20.These position values can be used to help generation of an image of theinner surface of heart 20 by a process of elimination, since any pointinside the heart, not in contact with the surface, is not on its innersurface.

[0200] As can be appreciated, contact between tip 74 and heart 20 mustbe assured. In particular, it is important to know when tip 74 comesinto contact with heart 20 after repositioning of tip 74 and thestability of tip 74 at a location, such as whether tip 74 moves fromlocation 75 without operator intervention as a result of motion of heart20 must be known. One method of monitoring the contact between tip 74and location 75 is through analysis of the trajectory of tip 74. Theinner wall of heart 20 has many crevices and tip 74 typically lodges inone of these crevices, such that tip 74 moving together with location75. It can be expected that tip 74 will return to the same spatialposition each cardiac cycle. Thus, if tip 74 does not return to the sameposition each diastole, contact between tip 74 and location 75 is notstable. Further, some types of slippage can be detected by determiningwhether the entire trajectory of tip 74 substantially repeats itselfFurthermore, some types of slippage add artifacts to the trajectorywhich can be detected by comparing the trajectory against trajectoriesof nearby segments of the heart or against a model of the motion of theheart.

[0201] It is also known that initiation of contact between tip 74 andheart 20 causes artifacts in a locally measured electrogram. Thus, in apreferred embodiment of the invention, tip 74 includes an electrode 79which measures the local electrical activity. Artifacts in the measuredactivity indicate that tip 74 is not in stable contact with location 75.Preferably, the local electrical activity and in particular, the localactivation time and local plateau length, are stored in association witheach location in heart 20.

[0202] In an additional embodiment of the invention, the contactpressure between tip 74 and location 75 is measured, using a pressuresensor, to determine the existence and stability of contacttherebetween.

[0203] In a preferred embodiment of the invention electrode 79 is usedto measure the impedance between tip 74 and a ground outside the patientThe impedance between tip 74 and the ground is affected by the distanceof tip 74 from the wall of heart and by the quality of contacttherebetween. The effect can be explained in the following manner. Longcells such as muscle cells and nerves exhibit electrical conductivitieswhich are non-isotropic and frequency dependent Blood, which fills heart20, exhibits conduction which is relatively frequency independent andisotropic, and its resistance is approximately half the averageresistance of muscle tissue. The greatest amount of frequency dependenceof body structures is found between 30 and 200 Hz. However, frequenciesin the range 30 Hz-10 MHz are useful. For example, at 50 KHz, contactcan be most easily determined from changes in the impedance and at 0.5MHz, accumulation of residue on the catheter from charring of heartmuscle during ablation can be determined from changes in the impedance.

[0204]FIG. 8 is a generalized graph showing the dependence of aresistance, between tip 74 and an external lead attached to the patient,on the distance of tip 74 from location 75, at 50 KHz.

[0205] Local geometric changes in the heart are also clinicallyinteresting. FIG. 9A shows a segment 90 of heart 20 and FIGS. 9B-9D showvarious aspects of local movement of segment 90. The timing of movementof segment 90 relative to the cardiac cycle and/or relative to themovement of other segments of heart 20 indicates forces acting atsegment 90. These forces may be as a result of local contraction atsegment 90 or as a result of contraction of other portions of heart 20.Movement of segment 90 before an activation signal reaches segment 90may indicate that segment 90 is not activated at an optimal time and,thus, that it does not contribute a maximum amount to the output ofheart 20. Movement without an activation signal usually indicatesnon-muscular tissue, such as scar tissue. The activation time ispreferably measured using electrode 79 (FIG. 6).

[0206]FIG. 9B shows another way of determining the reaction of muscletissue to an activation signal. A first location 92 is located adistance D1 from a second location 94 and a distance D2 from a thirdlocation 96. In a normal heart D1 and D2 can be expected to contract atsubstantially the same time by a substantially equal amount However, ifthe tissue between location 92 and location 94 is non-reactive, D1 mighteven grow when D2 contracts (Laplace's law). In addition a time lagbetween the contraction of D1 and of D2 is probably due to blocks in theconduction of the activation signal. A map of the reaction of the heartto an activation signal may be as important as an activation map, sinceit is the reaction which directly affects the cardiac output, not theactivation.

[0207]FIGS. 9C and 9D show the determination of local changes in theradius of heart 20, which can be together with the pressure to determinethe local tension using Laplace's law. In FIG. 9C a plurality oflocations 98, 100 and 102 exhibit a local radius R1 and in FIG. 9D, thelocal radius decreases to R2, which indicates that the muscle fiber atlocations 98, 100 and 102 is viable. It should be noted, that since thepressure in heart 20 is spatially equalized, a ratio between the tensionat different parts of heart 20 can be determined even if an absolutevalue cannot be determined.

[0208] In a preferred embodiment of the invention, a plurality ofcatheters are placed at locations 98, 100 and 102, so that changes inthe local geometry can be determined in a single cardiac cycle.Alternatively or additionally, a multi-head catheter, each head having aposition sensor, is used to map local geometrical changes. FIG. 10 showsa multi-head catheter 104 having a plurality of position sensors 106 formapping local geometric changes.

[0209] Another clinically important local change is a change in thethickness of a wall segment of heart 20. Muscle fibers thicken when theycontract, so an increase in the thickness of the wall segment indicatesthat muscle fibers in the wall segment are contracting. Thinning of thewall segment indicates that the wall segment is stretching. Either thereare not enough muscle fibers in the wall segment to overcome the tensionon the wall segment or the muscle fibers in the wall segment are notactivated in synchrony with the rest of heart 20, resulting in pressureincreases which are not counteracted by local tension increases. Lateincreases in the thickness of the wall segment usually indicate that theactivation signal was delayed at the segment. Local changes in thicknesscan also be compared to a locally determined activation time, todetermine a local reaction time. In addition, comparison of differencesin thickening between several adjacent wall segments is indicative ofthe activation time, much like changes in local geometry.

[0210] The local thickness of the wall segment is preferably determinedusing an ultrasonic sensor mounted on catheter 72 or catheter 78.Forward looking ultrasonic sensors (FLUS), suitable for mounting oncatheter 72 for determining the local thickness of the wall segment aredescribed in PCT application US95/01103 and in U.S. Pat. No. 5,373,849,the disclosures of which are incorporated therein by reference. A sidelooking ultrasonic sensor (SLUS), suitable for mounting on catheter 78is described in PCT publication WO 95/07657, the disclosure of which isincorporated herein by reference. Alternatively or additionally, anexternal sensor, such as an echocardiograph determines the thickness ofthe wall segment adjacent tip 94.

[0211] In a preferred embodiment of the invention sensors, additional toposition sensor 76, are mounted at tip 74. As already described, atleast one electrode 79 is preferably mounted at tip 74 to map the localelectrical activity which can be integrated with the geometric map toform an electro-mechanical map. For example, contraction duration can becompared to local electrical plateau length or local activation time canbe compared to local reaction time using an electro-mechanical map.

[0212] Additionally or alternatively, a chemical sensor is mounted attip 74 to determine changes in the local ionic concentrations or localchemical concentrations. Typically, such a chemical sensor is mounted ona needle which is inserted into the myocardium.

[0213] Alternatively or additionally, a perfusion meter is mounted ontip 74 to determine the amount of perfusion. Examples of perfusionmeters include: a Doppler ultrasound perfusion meter or a Doppler laserperfusion meter, such as disclosed in “Design for an ultrasound-basedinstrument for measurement of tissue blood flow”, by Bums, S. M. andReid, M. H., in Biomaterials. Artificial Cells and Artificial Organs,Volume 17, Issue 1 page 61-68, 1989, the disclosure of which isincorporated herein by reference. Such a perfusion meter preferablyindicates the flow volume and/or the flow velocity.

[0214] Alternatively or additionally, a scintillation detector ismounted on tip 74 to detect radiation emitted by radio-pharmaceuticalsinjected into or ingested by the patient. If a suitable low energyradio-pharmaceutical is used, the scintillation detector will besensitive to radiation from portions of heart 20 substantially incontact with tip 74. For example, local perfusion can be determined.

[0215] In another preferred embodiment of the invention, an opticalsensor is mounted on tip 74. As is known in the art, oxygenated bloodreflects a spectrum which is different from the spectrum reflected bynon-oxygenated blood. By determining the reflectance of portions ofheart 20, the perfusion thereof can be determined. Additionally oralternatively, optical reflectivity patterns or texture is used todifferentiate between different tissue types, for example, fibrous,viable muscle and damaged muscle. Preferably, the optical sensor is acamera or a fiber-optic image guide. Further preferably, an IR(infra-red) sensitive sensor is used. Typically, illumination at tip 74is provided by a light source mounted on tip 74 or by light transmittedthrough a fiber-optic light-guide.

[0216] Alternatively or additionally, a cold-tip catheter is used to mapthe effect of ablating a portion of the heart. It is known in the artthat hypothermic cardiac muscle does not initiate or react to electricalsignals. Cold-tip catheters, such as disclosed in PCT publication WO95/19738 of July 27, 1995, the disclosure of which is incorporatedherein by reference, can be used to inhibit the electrical activity of alocal wall segment while simultaneously mapping the local geometricaleffects of the inhibition.

[0217] Other locally sensed variables include, temperature, which mayindicate perfusion or activation, osmolarity, conduction velocity,repolarization time, repolarization duration, and impedance, which mayindicate tissue type and viability.

[0218] Mapping is typically performed when heart 20 is externally paced,such as using another catheter, either to set a constant heart rate orto generate certain arrhythmias. Electrode 79 is useful in identifyingand analyzing arrhythmias. In addition electrode 79 can be used as apacemaker to determine the effect of pacing from a certain location,such as initiating VT. The location of the catheter may be displayed asa relatively fixed location, such as end diastolic position.Alternatively, the movement of the catheter with the cardiac cycle isshown (with or without a changing map of the heart) as a navigationalaid.

[0219] Several types of maps are generally acquired. One type maps localphysiological values as a function of location on the heart, for exampleconductance. In this type of map, the position of tip 74 is typicallydetermined at the same phase of the cardiac cycle for each new locationand is unrelated to the acquisition of the local value. The local valuemay be time dependent. For example, a map of the instant local thicknessof the heart wall as a function of the phase of the cardiac cycle.Another example is a local electrogram as a function of time. The valuemay be continuously acquired over the entire cardiac cycle, only over aportion thereof or at a single instant synchronized to the positiondetermination and/or the cardiac cycle. A geometric map includesinformation about the geometry of the heart, for example shape andvolume, and/or changes in the geometry of the heart as a function oftime, for example, thickness, local curvature and shape. Anelectro-mechanical map includes information about the coupling betweenelectrical signals and mechanical changes in the heart, for example,thickening as a function of activation time. Other types of maps includechemical-mechanical maps, which correlate mechanical and chemical actionof the heart, energy expenditure maps which show local expenditures ofenergy, perfusion maps which show local perfusion of cardiac muscle anda map of the ratio between energy expenditure and local perfusion. Oneimportant type of map displays the delay between electrical activationtime and various parameters of mechanical reaction. The mechanicalreaction displayed may be a start of contraction, a maximum contractionor an end of contraction. Further, such a map may show the relativedelays between any portion of the local electrical activity and themechanical activity, for example, the electrical activity may be the endof the plateau or the beginning of the rapid depolarization. Thisinformation is useful in differentiated between healthy and diseasedtissue, as the lag between electrical and mechanical activity tends tobe more pronounced in diseased tissue.

[0220] Several different types of analysis are useful in preferredembodiments of the invention. In one, basic type of analysis,acquisition of local information is repeated at the same point over anumber of cycles for binning. Preferably, the pacing of the heart ischanged between the acquisitions and each measured value is associatedwith a particular pacing regime. Alternatively, this type of analysismay be practiced while performing ablations in the heart or otherwisechanging the activation profile of the heart. Alternatively, theacquired values are averaged over several cardiac cycles to reducenoise.

[0221] In accordance with another preferred embodiment of the invention,the trajectory of the catheter is analyzed over a period of severalcardiac cycles. This analysis is useful to determine changes in theactivation profile of the heart over time or as a function ofrespiration and body position.

[0222] In a preferred embodiment of the invention, one or more differenttypes of local analysis may be performed to assess cardiac function,locally and as a whole. One type of local analysis determines thelocation, velocity and or acceleration of the probe as a function of thecardiac cycle. Also, local voltage or any other type of localinformation may be used instead of position information. Such localinformation is expected to form a loop of values, where the values risesand/or lowers as a function of the cardiac cycle and returns tosubstantially the same value at the same phase of every cycle. In somediseased tissue, the loop may close (i.e., return to the same value atthe same phase) only after several cycles. The stability of these loopsis another indicator of cardiac health. The form of the loop may becompared between different locations to assess the relationship betweenthe local information values and electrical activation time, mechanicalactivation and other indicators of the action potential, including theplateau start and end.

[0223] In accordance with a preferred embodiment of the invention, localmechanical activation and/or other local mechanical activity, such asthe end of the contraction, may be determined based on a change in thevelocity direction or in the acceleration direction at a location. Itshould be appreciated that the velocity and acceleration may be referredto as three dimensional vectors in space or as simple one dimensionalvectors. Thus, one map in accordance with a preferred embodiment of theinvention, graphs changes in the velocity and acceleration profile as afunction of the movement of the catheter.

[0224] Another type of map in accordance with a preferred embodiment ofthe invention, shows the absolute peak-to-peak voltage at each location.In healthy tissue the value of this voltage may be one or more orders ofmagnitude higher than in scar tissue, with diseased tissue havingintermediate values. Thus, different types of cardiac tissues may beidentified based on the measured peak-to-peak voltage.

[0225] Another type of analysis relates to changes in area at alocation. In a preferred embodiment of the invention, the surface of theheart is reconstructed using a star based algorithm, as polygons,preferably triangles, with each point being a location. The areasurrounding a location is defined as the area in the polygons whichinclude the location. One type of map in accordance with a preferredembodiment of the present invention shows the changes in the areasurrounding the location as a function of time. The area generallyindicates local contractile performance. Another type of analysis isdetermining warping of the polygons as a function of the cardiac cycle.This analysis can be used to calculate stress and/or strain at thelocation.

[0226] In a preferred embodiment of the invention, maps are comparedbefore and after a medical procedure to assess its success. In addition,it may be desirable to compare maps taken at different times and atdifferent levels of cardiac activity and demand, for example, before,during and after exercise. In some patients it may not be practical toperform exercise, so a chemical, test, such as using Dobutamine, may beapplied instead of a physical stress test.

[0227] As explained above, maps can be used to determine clinicalinformation about the heart. Preferably, maps are constructed andanalyzed in preparation for a therapeutic procedure or in assessing thesuccess of a therapeutic procedure. For example, scar tissue neitherreacts to nor conducts an electrical signal, while hibernating muscletissue conducts the activation signal but does not react to it. A map,as described above, can be used to differentiate between these and othertypes of tissue.

[0228] Aneurysms are readily detectable on a geometric map, as bulgesduring systole. Furthermore, potential aneurysms can be detected soonafter an AMI (acute myocardial infraction) from local reactions to anactivation signal and local reactions to changes in intra-cardiacpressure, even if they are not visible to the naked eye. Automaticdetection may be based on paradoxical movement, in which anover-stressed portion of the heart expands (and bulges out) when theheart contracts and contracts when the heart expands.

[0229] The maps can be used to improve pumping efficiency of the heart.In an efficiently operating heart, each heart segment has an optimalrelation between its activation time and the cardiac cycle. Using one ofthe above described maps, the relationship between the local activationtime and the cardiac cycle can be determined. Using a finite-elementmodel of the heart as a pump, underutilized segments of the heart can bedetermined. The potential for improvement in the heart output can bedetermined from the model and different methods of improving heartfunction, such as described below, can be tested.

[0230] A preferred embodiment of the invention provides a solution tomapping when heart 20 has a non-constant rate. In one case, the heartrate varies, however, it is not arrhythmic. In this case, each heartbeat may be treated as one time unit, with an appropriate scaling. Whereheart beat is arrhythmic, either naturally, or by choice (manualpacing), position and other sensed values are binned according to ECG orelectrogram morphology, beat length, activation location, relativeactivation time or other determined cardiac parameters. Thus, aplurality of maps may be constructed, each of which corresponds to onebin. FIG. 11 is a flowchart of a preferred binning method. Localinformation is acquired simultaneously with an associated 12 lead bodysurface ECG. The morphology of the acquired ECG is correlated with aplurality of stored ECG traces. The local information is stored in a binwhich has the highest correlation. Preferably, if the correlation isbelow a predetermined limit, a new bin is created having the acquiredECG as its associated ECG.

[0231] It should be appreciated that locally determined characteristics,such as local electrogram, are associated with a particular segment ofheart 20, so that local twisting, moving and contractions can bedetermined. In many prior art systems, a map of the electrical activityof heart 20 is not associated with specific segments of heart 20 butwith general features.

[0232] A preferred embodiment of the invention utilizes adaptivemechanisms of the human heart to change the heart, in particular thedistribution of muscle mass in the heart.

[0233] A general property of muscle tissue, including cardiac muscle, isthat muscle tissue hypertrophies in reaction to increased stress andatrophies in reaction to reduced stress. According to a preferredembodiment of the invention, the stress and/or workload in the heart areredistributed to affect the distribution of cardiac muscle mass.Preferably, redistribution of stress and/or workload is achieved bychanging the location of pacing in the heart. Muscle tissue that isactivated sooner has a longer plateau, and as a result has a longerworking time. Muscle which is activated later has a greater initialcontractile force (due to its longer initial length caused by the raisein intra-cardiac pressure), but has a shorter plateau and a shorterworking time, which mean lower workload. Thus, workload can beredistributed by changing the pacing location.

[0234] It should be noted that increasing the plateau duration of amuscle segment can cause both atrophy and hypertrophy of the musclesegment. In general, increasing the plateau duration increases the boththe amount of work performed by the muscle segment and the force thatthe muscle exerts. As a result, the muscle segment may atrophy. However,if the muscle is diseased, the exerted force may not be increased.Further, changing the activation time may reduce the effectiveness ofthe muscle, so that it hypertrophies, even if the plateau duration wasincreased. Further, it may be desirable to activate a muscle portionearly and/or to extend its activation duration so that better perfusedmuscle will take over the work of less perfused muscle. Thus, even ifthe contractile force exerted by the muscle is increased by the increasein plateau duration, this increase is not sufficient to compensate forthe increase in workload requirement, with the result that the musclehypertrophies. Also, since the extent of ionic currents is usuallydifferent in healthy and diseased hearts, the effect of changing theplateau duration may be different.

[0235] Local uncompensated stress is caused by an increase inintra-cardiac pressure before the muscle is activated (to compensate).In healthy tissue, this stress results in a small amount of stretching,however, in weakened tissue, the stretching may be considerable andcause damage to the muscle. Since changing the pacing affects the amountof local stress which is not compensated for by muscle contraction,stress can also be redistributed by changing the pacing.

[0236]FIG. 12A shows a heart 20′ having a hyper trophied ventricularseptum 109. The activation of the left ventricle of heart 20′ typicallystarts from a location 108 at the apex of heart 20′, with the resultthat the activation times of a location 110 in an external wall 111 issubstantially the same as the activation time of a location 112 inseptum 109. If the initial activation location is moved from location108 to location 112, e.g. by external pacing, septum 109 will be moreefficiently utilized, while wall 111 will be activated later in thesystole, resulting in a shorter plateau duration of wall 111. As aresult, wall 111 will hypertrophy and septum 109 will atrophy, which isa desired result. It should be appreciated, that not all pathologicalchanges in muscle-mass distribution are reversible, especially ifslippage of muscle fibers and/or formation of scar tissue are involved.

[0237] Another preferred embodiment of the invention relates to changingthe activation profile of the heart in order to reduce the stress oncertain portions of the heart. FIG. 12B shows a heart 20″ having apartially infarcted portion 114. portion 114 has less muscle mass thanother parts of wall 111 and, in addition, may be activated later in thecardiac cycle than optimal. As a result, an aneurysm can be expected toform at portion 114. Pacing at location 116, with or without pacing atlocation 108, both stimulates the existing muscle tissue at portion 114and, since portion 114 is always contracted when other portions of theleft ventricle are contracting, reduces the chances of stretching.

[0238] Instead of redistributing stress, other local physiologicalvalues can redistributed, for example, a local oxygen requirement. As iswell known, the local oxygen requirement is directly related to thelocal workload. In some diseased hearts, the coronary arteries perfusinga first portion of the heart are more limited in their oxygenationcapability than the coronary arteries perfusing a second portion of theheart. In a patient suffering from chronic ischemia in the first portionof the heart, it may be advantageous to redistribute the workload sothat the first portion has less workload and the second portion has moreworkload. FIG. 12C shows heart 20″ having a first portion 120 thatsuffers from chronic ischemia and a second portion 122 that is welloxygenated. If the pacing of the left ventricle of heart 20″ is movedfrom its normal location 108 to a location 124, portion 122 takes overpart of the workload of portion 120.

[0239] Another type of redistribution relating to perfusion utilizes thefact that the coronary muscle perfuses best during diastole. In a hearthaving long conduction pathways, some portions may have a very latesystole and, as a result, be poorly perfused. In a preferred embodimentof the invention, late activated portions of the heart are paced so thatthey are activated earlier and, as a result, are better perfused.

[0240] As can be appreciated, many physiological values can beredistributed in a more optimal manner by correctly pacing the heart. Inparticular, local physiological values can be kept within a preferredrange by temporal or spatial redistribution. For example, by pacing oncefrom a first location and once from a second location, the averagestress at the first location can be equalized to the average stress atthe second location.

[0241] Another aspect of the present invention relates to optimizing aglobal parameter of cardiac operation (physiological variable), forexample, increasing the cardiac efficiency which ultimately increasesthe cardiac output and may reduce hypertrophy. The amount of workactually performed by a cardiac muscle segment is dependent on itsplateau length (which is dependent on its activation time) and on thecorrect sequencing of activation of different muscle segments. In anextreme case, a healthy portion of the heart is not activated at allduring the cardiac cycle due to a conduction block. In a preferredembodiment of the invention, the output of the heart is increased bychanging the activation profile of the heart to better utilize theexisting muscle tissue.

[0242]FIG. 12D shows heart 20″ having a substantially inactive musclesegment 126 which is closer to natural pacing location 108 of the leftventricle and a healthy muscle segment 130 which is further away frompacing location 108. Muscle segment 130 is not called upon to perform asmuch work as it can because of its late activation time, on the otherhand, segment 126 cannot perform as much work as it should since it isinfarcted. pacing the left ventricle from location 128 transfers thedemand from segment 126 to segment 130, which is able to answer thedemand. As a result, the output and efficiency of heart 20″ increase. Ifheart 20″ hypertrophied to compensate for its reduced output, thehypertrophy may be reversed. Other compensatory mechanisms, such asincreased heart rate may also be reversed, resulting in less stress onheart 20″.

[0243] It should be appreciated that changing the pacing location alsoaffects the utilization of ventricular septum 30. Using a multi-locationpacing scheme it is possible to pace at location 128 and simultaneouslypace ventricular septum 30, so that it is properly utilized.

[0244] Other cardiac physiological variables can also be optimized usingthe methods of the present invention. For example, by changing theactivation profile of the heart, the pressure gradient of the heart canbe matched to the impedance of the circulatory system. For example,hypertrophy is an adaptive mechanism for hardening arteries. Theincrease in size of the left ventricle results in a less pulsile flowwhich more readily enters the hardened arteries. By changing theactivation profile of the heart, the pulse can be made less pulsilewithout hypetrophy. Other variables which may be optimized include, butare not limited to, heart rate, diastolic interval, long axis and/orshort axis shortening, ejection fraction, valvular cross-sectional area,and parameters of the vascular system, such as blood volume andvelocity, blood-vessel cross-sectional area and blood pressure. Itshould be appreciated that such a variable may have a single value or ahave a continually changing value whose profile is to be optimized.

[0245] In an additional embodiment of the invention, the activationprofile of the heart is changed to reduce the maximum intra-cardiacpressure. Although such a reduction typically reduces the heart output,it may be lifesaving in case of an aortic or cardiac aneurysm.

[0246] Pacing the heart in the above described embodiments of theinvention can be performed in many ways. One pacing method does notrequire implanting a cardiac pacemaker. Rather, the conduction pathwaysin the heart are mapped and several of the pathways are disconnected topermanently change the activation profile of the heart.

[0247] Disconnecting the pathways can be achieved by surgically removingportions of pathways or by ablating those portions, using methods knownin the art. Alternatively, new conduction pathways can be formed in theheart, by surgically connecting pathways, by implanting conductivetissues or by implanting electrical conductors. For example, anelectrical lead having a distal end and a proximal end, which are bothhighly conductive, and which can act as a conduction pathway.Optionally, the lead includes a miniature circuitry which charges acapacitor with the plateau voltage from the proximal end and dischargesthe voltage as an activation signal at the distal end.

[0248] Alternatively, a pacemaker can be implanted. Typically, the AVnode is ablated and the ventricle is paced as described hereinabove.Alternatively, the AV node is not ablated, the SA node activation signalis sensed and the ventricles are activated artificially before thesignal from the AV node arrives at the ventricles. In some embodimentsof the invention, such as those explained. with reference to FIG. 12B,pacing can proceed in parallel both through the natural pathways andthrough the artificial ones, with similar beneficial results.

[0249] It should be appreciated that the use of multi-electrodepacemakers widens the variety of possible activation profiles andenables a better optimization. In particular, activation times can bemore precisely controlled using a multi-electrode pacemaker. Also, thelocal plateau length can be better controlled when using multi-locationpacing.

[0250] Another preferred embodiment of the invention provides apacemaker utilizing one of the above described pacing methods. In suchan embodiment, the pacemaker includes sensors for determining the stateof global or local cardiac parameters. For example, the intra-cardiacpressure can be monitored, and if it exceeds a certain amount, thepacing regime is changed to effect a change in the activation profile,which in turn affects the intra-cardiac pressure. In another example,the pacemaker measures the stress in certain segments of the heart, andif the stress in one of the segments exceeds a certain limit, the pacingregime is changed so that the stress in the segment is reduced.

[0251] In a preferred embodiment of the invention s the pacemakerdetermines local ischemic conditions, by measuring an injury current. Asis known in the art, when the activity of a segment of muscle tissue isimpaired, such as by oxygen starvation, the local voltage at rest ishigher than in normal muscle. This change in voltage can be directlymeasured using local sensors. Alternatively, isotonic currents caused bythe voltage difference can be measured. Further alternatively, theeffect of the voltage changes on an ECG, which are well known in theart, can be utilized to diagnose an ischemic condition.

[0252] In an additional embodiment of the invention, the pacing regimeis changed so that the stress is temporally redistributed betweendifferent segments of the heart. This type of distribution may berequired if a high cardiac output is required and most of the heart ischronically ischemic. By cycling the workload, each portion of the heartgets a recuperation period. A temporal redistribution may also berequired if it is not possible to efficiently activate two portions ofthe heart simultaneously, but activation of both is desired so thatneither one atrophies as result of non-use.

[0253] In a preferred embodiment of the invention, portions of heart 20are exercised by changing the pacing temporarily to increase theworkload, stress or other local values. After a short time, the pacingis returned to a previous regime, which demands less of the exercisedportions of heart 20.

[0254] There are several ways in which an optimal activation profile andits optimal pacing regime can be determined. In one preferred embodimentof the invention, a map of the heart is constructed and analyzed todetermine an optimal activation profile. Such determination is usuallyperformed using a model of the hear t such as a finite-element model. Itshould be appreciated that a relatively simple map is sufficient in manycases. For example, an activation-time map is sufficient for determiningsome portions of the heart which are activated too late in the cardiaccycle and are, thus, under utilized. In another example, A map ofthickness changes is sufficient to determine portions of the heart whichare inactive and/or to detect aneurysms.

[0255] Additionally or alternatively, an iterative method is used. Afirst pacing regime may be determined by analyzing a map or by heuristicmethods. After application of the pacing regime, an optimizationvariable or a distribution of a local variable are measured and thepacing regime changed appropriately. The cycle length of an iterationmay be very short, such as for an optimizing pacemaker. In muscle massredistribution, for example, the determination of the final pacingregime may take longer. First an initial pacing regime is determined fora heart diseased with HCM, after two or three weeks the heart is imagedand the improvement in the condition is determined. Based on themorphological changes in the heart a new pacing regime may bedetermined. This may be changed a number of times.

[0256] A preferred embodiment of the invention relates to optimalplacement of pacemaker electrodes. In the past, when a pacemaker isimplanted in a heart, the location of the electrodes is determined basedon one of the following factors:

[0257] (a) the quality and stability of the electrical contact betweenthe electrodes and the heart;

[0258] (b) the existence of artifacts in the electrogram; and

[0259] (c) the effect of the electrode placement and activation timing(for multi-electrode pacemakers) on the heart rhythm.

[0260] It should be noted, that since pacemaker electrodes are typicallyimplanted using a fluoroscope, the precision of their placement is low.In a preferred embodiment of the invention, pacemaker electrodeplacement and/or the pacing regime of the pacemaker are determined suchthat at least one cardiac parameter or the distribution of localphysiological values is optimized, as described above.

[0261] In a further preferred embodiment of the invention, an electrodeis test-implanted, or simulated by pacing from a catheter, in each of aplurality of electrode locations and the heart output associated witheach pacing location is measured. After determining the pacing locationwhich yields the highest cardiac output, the electrode is implanted inthat location. Preferably, the electrode is mounted on a positionsensing catheter to aid in repositioning of the electrode. Preferably,the catheter comprises a peelable sheath enclosing the electrodes, wherethe sheath contains at least one position sensor. Further preferably, asteerable catheter is used. Preferably, the operation of the heart isre-evaluated after one or two weeks to determine the effect of thecardiac-adaptation mechanisms on the position of the optimal pacingposition. If necessary, one or more electrodes are moved. Alternativelyor additionally, when a multi-electrode pacemaker is used, the pacinglocation can be changed by activating alternative electrodes.

[0262]FIG. 13 shows an implanted pacemaker according to a preferredembodiment of the invention. A control unit 140 electrifies a pluralityof electrodes 142 implanted in various locations in heart 20″, inaccordance with at least one of the pacing regimes described above.Various local physiological values of the heart can be determined usingelectrodes 142, for example, local activation time and plateau length.Alternatively or additionally, at least one implanted sensor 146 is usedto determine local physiological values, such as perfusion andthickness. Alternatively or additionally, a cardiac physiologicalvariable is measured using a sensor 144. Examples of physiologicalvariables include, the intra-cardiac pressure which may be measuredusing a solid state pressure transducer and the stroke volume, which maybe measured using a flow velocity sensor in the aorta. Other variablesinclude: heart rate, diastolic interval, long and short axis shortening,ejection fraction and valvular cross-section. In addition, vascularvariables may be measured in any particular vessel, for example,blood-vessel cross-section, vascular flow velocity, vascular flow volumeand blood pressure. Any one of these variables can be used to asses thefunctionality of the heart under a new pacing regime.

[0263] It should be appreciated that cardiac mapping can be performedboth from the inside of the heart by inserting a catheter into the heartand from the outside of the heart by inserting the catheter into thecoronary veins and arteries. Further, mapping, especially electricalmapping, can be performed inside the heart muscle, such as by insertingan electrode carrying needle into the muscle.

[0264] Cardiac mapping in accordance with preferred embodiments of theinvention, is preferably performed using the Carto system (forelectrical mapping) and the Noga system (for electromechanical mapping),both available form Biosense (Israel) Ltd., Tirat HaCarmel, Israel. Somepreferred types of mapping catheters are described in a PCT applicationfiled in Israel on Jan. 8, 1997, by applicant “Biosense” and titled“Mapping Catheter”, the disclosure of which is incorporated herein byreference.

[0265] It should also be appreciated that once the position of thecatheter is known, external sensors can be used to provide localphysiological values of heart tissue adjacent to the tip of the sensor.For example, if the tip of the catheter caries an ultra-sound marker, anultrasound image including the marker can be used to determine the localwall thickness. Another example is a combination with SPECT (singlephoton emission tomography). If the catheter incorporates a radioactivemarker suitable for SPECT, local functional information can be gleanedfrom a SPECT image. Yet another example is determining local perfusionfrom Doppler-ultrasound images of the coronaries, from nuclear medicineimages or from X-ray or CT angiography and overlaying the perfusion mapon the geometrical map. In general, a map in accordance with the presentinvention may be overlaid on or combined with many types of medicaldata, for example three-dimensional CT data and the like.

[0266] One method of aligning an angiogram or a perfusion map with acatheter-acquired map is to acquire both maps substantiallysimultaneously. The image of the catheter in the perfusion map can thenbe used to determine if the catheter is near a perfused tissue ornon-perfused tissue. Alternatively or additionally, a plurality ofreference locations are identified in both the catheter-based map andthe perfusion map, so that the two maps can be aligned. The referencelocations can be locations either inside or outside the body and theymay be identified by placing a position-sensing sensor at the locationduring the catheter-based mapping. Preferably, the reference locationsare also identified during the perfusion mapping by using aposition-sensitive sensor, so that the frames of reference for the twomaps can be automatically aligned, for example, using the referencecatheter as described above. Alternatively or additionally, anappropriate type of radio-opaque or radiative marker is placed on thebody so that it is visible during the perfusion mapping. Alternatively,the reference locations are identified from anatomical or functionaldetails in the two maps.

[0267] It should be appreciated that a two dimensional angiogram can bealigned, in a clinically useful manner, with a two-dimensionalprojection of a map of the heart. The appropriate projection directioncan be determined from the relative positions of the patient and theangiographic system during the angiography. Preferably, a bi-planeangiogram is aligned with two two-dimensional projections of a map ofthe heart, alternatively, other types of angiograms or perfusion mapsare used. Alignment may be automatic, using fiduciary marks or referencelocations as described above. Alternatively, manual alignment oranalysis is performed.

[0268] It should be appreciated that a catheter can be positioned inalmost any part of the body via the vascular system and via bodyorifices. In addition, a positioning sensing catheter can be surgicallyinserted in any portion of the body, for example, inserting the catheterinto the abdomen or into the thigh. Thus, the above described mappingand pacing (stimulating) methods and apparatus can also be applied tomapping and stimulating atrophied and injured muscles, mapping thebowels and mapping the electrical and chemical activity of the brain.

[0269] The present invention has been described in a plurality ofpreferred embodiments, each of which has been separately described. Itshould be appreciated that the present invention contemplates combiningvarious aspects of different embodiments, for example, various types ofmappings and various types of pacing may be combined in accordance withpreferred embodiments of the invention. Further, many different types ofmapable local physiological variables have been described. In variouspreferred embodiments of the invention, any number of these variablesmay be mapped and their coupling analyzed to yield information about theactivity of a heart. The scope of the invention also includes apacemaker designed to or programmed to perform any of the abovedescribed pacing regimes. Further, the scope of the present inventionalso encompasses the act of programming a pacemaker to perform any ofthe above described pacing regimes and the act of modifying pulseparameters in accordance with any embodiment of the present invention.Also, the scope of the invention should be construed to includeanalyzing such maps, as described herein and apparatus, such as acomputer workstation with software, for performing such analyses. Inaddition the scope of the invention should be construed to includeapparatus for acquiring maps as described herein, and in particularsoftware suitable for converting individual local positions, sensedphysiological values and electrical activity into such maps. Also suchapparatus preferably displays such maps to an operator, either as a snapshot or as a dynamic map.

[0270] Another aspect of the present invention relates to computer aideddiagnosis. A library of maps representing different types ofpathologies, from many patients may be stored on a computer. Since themaps are typically acquired using a computerized system, inputting themaps is easy. When a patient is diagnosed, the diagnosis is stored alongwith the map, as well as any additional information, such as history,development of the disease, effects of various drugs (with maps to showthese effects), effect of new pacing regimes and the like. When a newmap is made, this map may be correlated with the maps in the library tomore easily diagnose the patient. Maps may be correlated usinganatomical landmarks, fiduciary marks inputted by the user, orgeometrical alignment. In addition a map may be correlated with aprevious map of the same patient to asses the success of a treatment. Ina preferred embodiment of the invention, the computer system include anexpert system which helps with the diagnosis and/or suggests anappropriate treatment. It should be appreciated, that even though eachperson may have a different anatomy and different cardiac disorders,there will be many similarities between maps of different people havingsimilar disorders, such as ischemia due to the blockage of a particularcoronary artery.

[0271] It will be appreciated by persons skilled in the art that thepresent invention is not limited to what has thus far been described.Rather the scope of the present invention is limited only by the claimswhich follow.

1. A method of constructing a cardiac map of a heart having a heartcycle comprising: (a) bringing an invasive probe into contact with alocation on a wall of the heart; (b) determining, at at least twodifferent phases of the heart cycle, a position of the invasive probe;(c) determining a local non-electrical physiological value at thelocation; (d) repeating (a)-(c) for a plurality of locations of theheart; and (e) combining the positions to form a time-dependent map ofat least a portion of the heart.
 2. A method according to claim 1,comprising: (f) determining at least one local relationship betweenchanges in positions of the invasive probe and a determined localnon-electrical physiological value.
 3. A method of constructing acardiac map of a heart having a heart cycle comprising: (a) bringing aninvasive probe into contact with a location on a wall of the heart; (b)determining a position of the invasive probe; (c) determining a localnon-electrical physiological value at the location at a plurality ofdifferent phases of the heart cycle; (d) repeating (a)-(c) for aplurality of locations of the heart; and (e) combining the positions toform a map of at least a portion of the heart.
 4. A method according toclaim 3, comprising determining at least a second position of theinvasive probe at a phase at which the local non-electrical value isfound, which position is different from the position determined in (b).5. A method according to claim 4, comprising determining at least onelocal relationship between changes in positions of the invasive probeand determined local non-electrical physiological values.
 6. A methodaccording to any of claims 1-5, comprising determining a trajectory ofthe probe as a function of the cardiac cycle.
 7. A method according toclaim 6, comprising analyzing the trajectory.
 8. A method according toany of claims 1-7, wherein the local physiological value is determinedusing a sensor external to the probe.
 9. A method according to claim 8,wherein the sensor is external to a body which comprises the heart. 10.A method according to any of claims 1-7, wherein the local physiologicalvalue is determined using a sensor in the invasive probe.
 11. A methodaccording to any of claims 1-10, wherein the local physiological valueis determined at substantially the same time as the position of theinvasive probe.
 12. A method according to any of claims 1-11, whereinthe map comprises a plurality of maps, each of which corresponds to adifferent phase of the cycle of the heart.
 13. A method according to anyof claims 1-11, wherein the map comprises a difference map between twomaps, each of which corresponds to a different phase of the cycle of theheart.
 14. A method according to any of claims 1-13, wherein the localphysiological value comprises a chemical concentration.
 15. A methodaccording to any of claims 1-14, wherein the local physiological valuecomprises a thickness of the heart at the location.
 16. A methodaccording to claim 15, wherein the thickness of the heart is determinedusing an ultrasonic transducer mounted on the invasive probe.
 17. Amethod according to any of claims 15-16, comprising, determining areaction of the heart to an activation signal by analyzing changes inthe thickness of the heart.
 18. A method according to any of claims1-17, wherein the local physiological value comprises a measure of aperfusion at the location.
 19. A method according to any of claims 1-18,wherein the local physiological value comprises a measure of workperformed at the location.
 20. A method according to any of claims 1-19,comprising determining a local electrical activity at each of theplurality of locations of the heart.
 21. A method according to claim 20,wherein the electrical activity comprises a local electrogram.
 22. Amethod according to claim 20 or claim 21, wherein the electricalactivity comprises a local activation time.
 23. A method according toclaim any of claims 20-22, wherein the electrical activity comprises alocal plateau duration of heart tissue at the location.
 24. A methodaccording to any of claims 20-23, wherein the electrical activitycomprises a peak-to-peak value of a local electrogram.
 25. A methodaccording to any of claims 1-24, comprising, determining a local changein the geometry of the heart.
 26. A method according to claim 25,wherein the local change comprises a change in a size of an areasurrounding the location.
 27. A method according to claim 25, whereinthe local change comprises a warp of an area surrounding the location.28. A method according to claim 25, wherein the local change comprises achange in a local radius of the heart at the location.
 29. A methodaccording to any of claims 25-28, comprising, determining anintra-cardiac pressure of the heart.
 30. A method according to claim 28or claim 29, comprising determining a relative tension at the location.31. A method according to claim 30, wherein the relative tension isdetermined using Laplace's law.
 32. A method according to any of claims25-29, comprising determining an absolute tension at the location.
 33. Amethod according to any of claims 1-32, comprising determining amovement of the location on the heart wall relative to the movement ofneighboring locations.
 34. A method according to any of claims 1-33,comprising determining the activity of the heart at the location.
 35. Amethod according to claim 34, wherein determining the activity comprisesdetermining a relative motion profile of the location on the heart wallrelative to neighboring locations.
 36. A method according to claim 34,wherein determining the activity comprises determining a motion profileof the heart at the location.
 37. A method according to any of claims1-36, comprising monitoring stability of the contact between theinvasive probe and the heart.
 38. A method according to claim 37,wherein monitoring comprises monitoring the stability of the contactbetween the probe and the heart based on the motion profile.
 39. Amethod according to any of claims 37-38, wherein monitoring comprisesdetecting changes in the motion profile for different heart cycles. 40.A method according to any of claims 37-39, wherein monitoring comprisesdetecting differences in positions of the probe at the same phase fordifferent heart cycles.
 41. A method according to any of claims 37-40,wherein monitoring comprises detecting changes in a locally measuredimpedance of the invasive probe to a ground.
 42. A method according toany of claims 37-41, wherein monitoring comprises detecting artifacts ina locally determined electrogram.
 43. A method according to any ofclaims 1-42, comprising reconstructing a surface of a portion of theheart.
 44. A method according to any of claims 1-43, comprising binninglocal information according to characteristics of the cycle of theheart.
 45. A method according to claim 44, wherein the characteristicscomprise a heart rate.
 46. A method according to claim 44 or claim 45,wherein the characteristics comprise a morphology of an ECG of theheart.
 47. A method according to claim 46, wherein the ECG is a localelectrogram
 48. A method according to any of claims 44-47, comprisingseparately combining the information in each bin into a map.
 49. Amethod according to claim 48, comprising determining differences betweenthe maps.
 50. A method according to any of claims 1-49, wherein thepositions of the invasive probe are positions relative to a referencelocation.
 51. A method according to claim 50, wherein the referencelocation is a predetermined portion of the heart.
 52. A method accordingto any of claims 50-51, wherein a position of the reference isdetermined using a position sensor.
 53. A method according to any ofclaims 50-52, comprising periodically determining a position of thereference location.
 54. A method according to claim 53, wherein theposition of the reference location is acquired at the same phase indifferent cardiac cycles.
 55. A method according to any of claims 1-54,wherein the invasive probe is located in a coronary vein or artery. 56.A method according to any of claims 1-54, wherein the invasive probe islocated outside a blood vessel.
 57. A method according to any of claims1-56, wherein local information is averaged over a plurality of cycles.58. A method of determining the effect of a treatment comprising:constructing a first map of a heart according to any of claims 1-56,prior to the treatment; constructing a second map of the heart, afterthe treatment; and comparing the first and second maps to diagnose theeffect of the treatment.
 59. A method comprising: constructing a map ofa heart according to any of claims 1-56; and analyzing the map todetermine underutilized portions of the heart.
 60. A method comprising:constructing a map of a heart according to any of claims 1-56; andanalyzing the map to select a procedure for treating the heart.
 61. Amethod comprising: constructing a map of a heart according to any ofclaims 1-56; and analyzing the map to determine optimizationpossibilities in the heart.
 62. A method comprising: constructing a mapof a heart according to any of claims 1-56; and analyzing the map todetermine underperfused portions of the heart.
 63. A method comprising:constructing a map of a heart according to any of claims 1-56; andanalyzing the map to determine over-stressed portions of the heart. 64.A method comprising: constructing a map of a heart according to any ofclaims 1-56; and analyzing the map to determine local pathologies in theheart.
 65. A method comprising: constructing a map of a heart accordingto any of claims 1-56; and analyzing the map to assess the viability ofportions of the heart.
 66. A method of determining the effect of achange in activation of a heart, comprising: constructing a first map ofa heart according to any of claims 1-56, prior to the change;constructing a second map of the heart, after the change; and comparingthe first and second maps to diagnose the effect of the change inactivation.
 67. A method of determining the effect of a change inactivation of a heart, comprising: constructing a first map of a heartaccording to any of claims 1-56, prior to the change; constructing asecond map of the heart, after the change; and constructing a second mapof the heart; and comparing the first and second maps, wherein the twomaps are acquired in parallel by acquiring local information at alocation over several cardiac cycles, wherein the activation changesduring the several cardiac cycles.
 68. A method of assessing viabilitycomprising: constructing a first map of a heart according to any ofclaims 1-56, prior to a change in activation of the heart; constructinga second map of the heart, after the change; and comparing the first andsecond maps to assess the viability of portions of the heart.
 69. Amethod according to any of claims 66-68, wherein changing the activationcomprises changing a pacing of the heart.
 70. A method according to anyof claims 66-68, wherein changing the activation comprises subjectingthe heart to chemical stress.
 71. A method according to any of claims66-68, wherein changing the activation comprises subjecting the heart tophysiological stress.
 72. A method according to any of claims 1-71,wherein the heart is artificially paced.
 73. A method of cardiac shapingcomprising: generating a map of a heart; choosing a portion of the hearthaving a certain amount of muscle tissue thereat; and determining apacing regime for changing the workload of the portion.
 74. A methodaccording to claim 73, comprising pacing the heart using the determinedpacing regime.
 75. A method according to claim 74, comprising: waiting aperiod of time; then determining the effect of the pacing regime; andrepeating choosing, determining and pacing if a desired effect is notreached.
 76. A method according to any of claims 73-75, wherein theworkload of the portion is increased in order to increase the amount ofmuscle tissue therein.
 77. A method according to any of claims 73-75,wherein the workload of the portion is decreased in order to decreasethe amount of muscle tissue thereat.
 78. A method according to any ofclaims 73-77, wherein the workload is changed by changing an activationtime of the portion.
 79. A method according to any of claims 73-78,wherein the map includes electrical activation information.
 80. A methodaccording to any of claims 73-79, wherein the map includes mechanicalactivation information.
 81. A method of determining an optimal locationfor implanting a pacemaker electrode comprising: (a) pacing a heart froma first location; (b) determining a cardiac parameter associated withpacing at the location; and (c) repeating (a) and (b) for a secondlocation; and (d) selecting an optimal location based on the determinedvalues for the cardiac parameters.
 82. A method according to 81,comprising: (e) implanting the electrode at the location for which thecardiac parameter is optimal.
 83. A method according to any of claims81-82, wherein pacing a heart comprises bringing an invasive probehaving an electrode to a first location and electrifying the electrodewith a pacing current.
 84. A method according to any of claims 81-83,wherein the cardiac parameter comprises stroke volume.
 85. A methodaccording to any of claims 81-84, wherein the cardiac parametercomprises intra-cardiac pressure.
 86. A method according to any ofclaims 81-85, wherein determining the cardiac parameter comprisesmeasuring the cardiac parameter using an invasive probe.
 87. A method ofdetermining a regime for pacing a heart, comprising: (a) determining alocal physiological value at a plurality of locations in the heart; and(b) determining a pacing regime which changes a distribution of thephysiological value in a desired manner.
 88. A method according to claim87, wherein the distribution comprises a temporal distribution.
 89. Amethod according to any of claims 87-88, wherein the distributioncomprises a spatial distribution.
 90. A method according to any ofclaims 87-88, comprising pacing the heart using the determined pacingregime.
 91. A method according to any of claims 87-90, wherein changingthe distribution comprises maintaining physiological values within agiven range.
 92. A method according to claim 91, wherein the rangecomprises a locally determined range.
 93. A method according to any ofclaims 91-92, wherein the range comprises a phase dependent range,whereby a different range is preferred for each phase of a cardiaccycle.
 94. A method according to any of claims 91-93, wherein the rangecomprises an activation dependent range, whereby a different range ispreferred for each activation profile of the heart.
 95. A methodaccording to claim 94, wherein different heart rates have differentranges.
 96. A method according to claim 94, wherein different arrhythmiastates have different ranges.
 97. A method according to any of claims87-96, wherein the physiological values are determined substantiallysimultaneously.
 98. A method according to any of claims 87-97, whereinthe physiological value comprises perfusion.
 99. A method according toany of claims 87-98, wherein the physiological value comprises stress.100. A method according to any of claims 87-99, wherein thephysiological value comprises plateau duration.
 101. A method ofdetermining a preferred pacing regime, comprising: generating a map ofthe heart; and determining, using the map, a preferred pacing regime fora heart which is optimal with respect to a physiological variable. 102.A method according to claim 101, comprising pacing the heart using thepreferred pacing regime.
 103. A method according to any of claims101-102, wherein the map comprises an electrical map.
 104. A methodaccording to claim 103, wherein determining a preferred pacing regimecomprises generating a map of the activation profile of the heart. 105.A method according to any of claims 101-103, wherein the map comprises amechanical map.
 106. A method according to claim 105, whereindetermining a preferred pacing regime comprises generating a map of thereaction profile of the heart.
 107. A method according to any of claims101-106, comprising analyzing an activation map or a reaction map of theheart to determine portions of the heart which are under-utilized due toan existing activation profile of the heart.
 108. A method according toany of claims 101-107, wherein pacing is initiated by implanting atleast one pacemaker electrode in the heart.
 109. A method according toclaim 108, wherein the at least one pacemaker electrode comprises aplurality of individual electrodes, each attached to a different portionof the heart.
 110. A method according to any of claims 101-109, whereinpacing is initiated by changing the electrification of a plurality ofpreviously implanted pacemaker electrodes.
 111. A method according toany of claims 101-110, wherein the physiological variable comprises astroke volume.
 112. A method according to any of claims 101-110, whereinthe physiological variable comprises a ventricular pressure profile.113. A method of pacing comprising: (a) pacing a heart using a firstpacing scheme; and (b) changing the pacing scheme to a second pacingscheme, wherein the change in pacing is not directly related to a sensedor predicted arrhythmia, fibrillation or cardiac output demand in theheart.
 114. A method according to claim 113, wherein each of the pacingregimes optimizes the utilization of different portions of the heart.115. A method according to claim 113 or claim 114, wherein the changingof the pacing regimes temporally distributes workload between differentportions of the heart.
 116. A pacemaker which performs a least onemethod according to any of claims 87-115.
 117. A pacemaker comprising: aplurality of electrodes; a source of electricity for electrifying theelectrodes; and a controller which changes the electrification of theelectrodes in response to a plurality of values of local information ofa heart, measured at different locations, to achieve an optimization ofa cardiac parameter of the heart.
 118. A pacemaker according to claim117, wherein the local information is measured using the electrodes.119. A pacemaker according to any of claims 117-118, wherein the localinformation is measured using a sensor.
 120. A pacemaker comprising: aplurality of electrodes; a source of electricity for electrifying theelectrodes; and a controller which changes the electrification of theelectrodes in response to a stored map of values of local information ofa heart at different locations, to achieve an optimization of a cardiacparameter of the heart.
 121. A pacemaker according to any of claims117-120, wherein the local information comprises a local activationtime.
 122. A pacemaker according to any of claims 117-121, wherein thelocal information comprises a local plateau duration.
 123. A pacemakeraccording to any of claims 117-122, wherein the local informationcomprises local physiological values.
 124. A pacemaker according to anyof claims 117-123, wherein the local information comprises phasedependent local positions.
 125. A pacemaker according to any of claims117-124, wherein the cardiac parameter comprises a stroke volume.
 126. Apacemaker according to any of claims 117-125, wherein the cardiacparameter is measured by the pacemaker.
 127. A pacemaker according toany of claims 117-126, wherein the cardiac parameter comprises anintra-cardiac pressure.
 128. A method of detecting structural anomaliesin a heart, comprising: (a) bringing an invasive probe into contact witha location on a wall of the heart; (b) determining a position of theinvasive probe; (c) repeating (a)-(b) for a plurality of locations onthe wall; (d) combining the positions to form a time-dependent map of atleast a portion of the heart; and (e) analyzing the map to determinestructural anomalies in the heart.
 129. A method according to claim 128,wherein the structural anomaly is an insipid aneurysm.
 130. A methodaccording to any of claims 128-129, comprising repeating (b) at least asecond time, at the same location and at a different phase of thecardiac cycle than (b).
 131. A method of adding a conductive pathway ina heart between a first segment of the heart and a second segment of theheart, comprising: generating a mechanical map of the heart; providingan activation conduction device having a distal end and a proximal end;electrically connecting the distal end of the device to the firstsegment; and electrically connecting the proximal end of the device tothe second segment.
 132. A conductive device for creating conductivepathways in the heart, comprising: a first lead adapted for electricalconnection to a first portion of the heart; a second lead adapted forelectrical connection to a second portion of the heart; a capacitor forstoring electrical charge generated at the first portion of the heartand for discharging the electrical charge at the second portion of theheart.
 133. A method of viewing a map, comprising: providing a map oflocal information of a heart; and overlaying a medical image on the map.134. A method according to claim 133, wherein the medical image is anangiogram.
 135. A method according to any of claims 133-134, wherein themedical image is a three-dimensional image.
 136. A method according toany of claims 133-134, wherein the map contains both spatial andtemporal information.
 137. A method of diagnosis comprising: generatinga map of a heart; and correlating the map with a library of maps.
 138. Amethod according to claim 137, comprising diagnosing the condition ofthe heart based on the correlation.
 139. A method of analysis,comprising: generating a map of electrical activation of a heart;generating a map of mechanical activation of the heart; and determininglocal relationships between the local electrical activation andmechanical activation.
 140. A method according to claim 139, wherein themechanical activation comprises a profile of movement.
 141. A methodaccording to any of claims 139-140, wherein the electrical activationcomprises an activation time.
 142. Apparatus adapted to generate a mapin accordance with any of claims 1-56.
 143. Apparatus according to claim142, comprising a display adapted to display the map.
 144. Apparatuscomprising: a memory having a plurality of maps stored therein; and acorrelator which correlates an input map with the plurality of maps.